This publication is Open Access under the license indicated. Learn More
ACS Editors' Choice® is a collection designed to feature scientific articles of broad public interest. Read the latest articles
Feature Article
Exploration of Reaction Pathways and Chemical Transformation NetworksClick to copy article linkArticle link copied!EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Gregor N. SimmGregor N. SimmLaboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, SwitzerlandMore by Gregor N. Simm
- Alain C. VaucherAlain C. VaucherLaboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, SwitzerlandMore by Alain C. Vaucher
- Markus Reiher*Markus Reiher*M. Reiher. E-mail: markus.reiher@phys.chem.ethz.chLaboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, SwitzerlandMore by Markus Reiher
Abstract
Click to copy section linkSection link copied!
For the investigation of chemical reaction networks, the identification of all relevant intermediates and elementary reactions is mandatory. Many algorithmic approaches exist that perform explorations efficiently and in an automated fashion. These approaches differ in their application range, the level of completeness of the exploration, and the amount of heuristics and human intervention required. Here, we describe and compare the different approaches based on these criteria. Future directions leveraging the strengths of chemical heuristics, human interaction, and physical rigor are discussed.
Copyright © 2018 American Chemical Society
1. Introduction
Click to copy section linkSection link copied!
For a detailed analysis of a chemical system, all relevant intermediates and elementary reactions on the potential energy surface (PES) connecting them need to be known. An in-depth understanding of all reaction pathways allows one to study the evolution of a system over time given a set of initial conditions (e.g., reactants and their concentrations, temperature, and pressure) and propose derivatives of the original reactants to avoid undesired side reactions. Manual explorations of complex reaction mechanisms employing quantum-chemical methods are slow and error-prone. Moreover, because of the high dimensionality of PESs, an exhaustive exploration is generally unfeasible. However, to rationalize the formation of undesired side products or decomposition reactions, unexpected reaction pathways need to be uncovered.
Complex reaction mechanisms are ubiquitous in chemistry. They are, for instance, the basis of transition-metal catalysis, (1) polymerizations, (2) cell metabolism, (3) enzyme catalysis (e.g., refs (4) and (5)), surface chemistry (e.g., refs (6−12)), and environmental processes (13) and are the objective of systems chemistry. (14) Knowing all chemical compounds and elementary reactions of a specific chemical process is essential for its understanding in atomistic detail. Even though many chemical reactions result in the selective generation of one main product, (15) in general, multiple reaction pathways compete with each other. A variety of side products may be generated by reactive species (such as radicals, valence-unsaturated species, charged reactants, strong acids and bases and so forth) or through high-energy (electronic or vibrational) states populated by light, elevated temperature, or increased pressure.
Some excellent reviews on the exploration of reaction pathways already exist (for recent ones see refs (16) and (17)). Our overview here, however, has a different focus and also extends the literature covered in previous reviews. We organize the plethora of strategies developed for the exploration of PESs into three classes (some protocols combine strategies from more than one class), which are illustrated in Figure 1.
Class 1: Starting from a point on the PES (indicated by the green region in Figure 1, left) new TS and intermediates are discovered by relying on local curvature information. This process is repeated (possibly in multiple directions) until all (relevant) stationary points of the PES are explored.
Class 2: Starting from a minimum energy structure, points on the PES (e.g., new intermediates or approximate TSs) are explored through the application of heuristics (guided by chemical rules as indicated by straight lines in the Figure 1, middle). This includes, for example, the formulation of graph-based transformation rules or the application of an artificial force pushing reactive moieties upon one another. Once a new intermediate is found, the minimum energy pathway (MEP) connecting it to the starting structure can be searched for.
Class 3: The strengths of human (chemical) knowledge and intuition can be combined with ultrafast computer simulations in an interactive setting to efficiently explore intermediates and TSs of a PES (Figure 1, right). This class has hardly been considered in previous reviews, which is why we discuss this class in some depth here.
Figure 1
Figure 1. General strategies for the exploration of PESs. Left: local curvature information on the PES is exploited to identify TSs and products. Middle: through the application of heuristics new intermediates are identified. Right: intermediates and TSs are explored interactively. In the two latter cases of heuristics-based and interactive explorations, pathways need to be refined a posteriori to obtain MEPs. An efficient exploration protocol may combine strategies from different classes.
For the accurate description of a chemical process, not only bond-breaking and bond-forming transformations are to be considered but also the conformational space of each intermediate must be explored. This is particularly critical for an accurate description of thermodynamic properties (e.g., Gibbs free energies) of compounds and for reactions in which multiple MEPs connecting the same configurational isomers can exist. In general, all exploration strategies mentioned above can be employed to locate conformational isomers. It should be noted, however, that in contrast to bond-breaking or bond-forming transformations, in most practical applications, TSs between conformers are not of interest as the time scale of a reaction can be assumed to be longer than the time required for the conformers to equilibrate. For a recent review on conformer generation see ref (18).
In the following three sections, we review algorithms assigned to the three classes. The approaches differ in the degree of automation possible (an aspect which is particularly critical for large reaction networks), the amount of heuristics required, and the degree of completeness of the exploration. Approaches involving little or no heuristics tend to explore the PES in a more systematic fashion. However, they are often limited by computational demands. By contrast, heuristics-driven methods can be applied to efficiently study larger chemical systems, although care must be taken in order not to compromise the thoroughness of the exploration by making strong assumptions about a system’s reactivity.
2. Class 1: Exploiting Curvature Information
Click to copy section linkSection link copied!
The manual construction of approximate TS candidates is slow, cumbersome, and highly unsystematic. Recent developments therefore focused on providing more streamlined and systematic means for the location of TSs. Ohno and Maeda exploited curvature information on the PES in a strategy called anharmonic downward distortion following (ADDF). (19−23) When a minimum structure is distorted in a way orthogonal to the potential energy contours, MEPs can be found. As a result, a path explored through ADDF is very close to the one obtained from an intrinsic reaction coordinate calculation. Repeated application of ADDF on newly explored intermediates yields all relevant MEPs. ADDF was successfully applied to reactions of small molecules such as formaldehyde, propyne, and formic acid. Recently, Satoh et al. (24) systematically explored conformational transitions of d-glucose by employing ADDF to trace only low TS barriers.
To address the limitations of ADDF, Maeda, Morokuma, and co-workers developed the artificial force-induced reaction (AFIR) method. (17,25−29) AFIR overcomes intermolecular activation energies by applying an artificial force pushing the reactants together. When optimization is performed under this biasing force, the maximum energy point lies close to the true TS. AFIR has been successfully applied to the Claisen rearrangement, (27,28) cobalt-catalyzed hydroformylations, (27,28) an aldol reaction, (28) and the Biginelli reactions. (30) A consequence of the algorithm is that many random initial orientations of the two reactants need to be sampled before all relevant pathways are found. In addition, human input will often be required to select pairs of reacting molecules to circumvent a combinatorial explosion and to work with the amount of data produced.
Another systematic approach to explore potential energy surfaces starting from some configuration of a reactive system is reactive molecular dynamics (MD) simulations, in which the Newtonian equations of motion are solved for the nuclei or atoms to explore and sample the part of configuration space that is accessible under the constraints imposed by a predefined thermodynamic ensemble. The force is either calculated as the negative gradient of a classical force-field potential energy model or of an electronic energy (in ab initio MD) evaluated with an approximate quantum chemical method (typically from semiempirical or density functional theory) for the configuration for which the force is needed for trajectory propagation. To increase the possibility of a reaction to occur, the temperature and pressure of a simulation often need to be increased, which in turn leads to the frequent occurrence of transformations that are unlikely under common laboratory conditions.
The capabilities of reactive ab initio molecular dynamics for studying complex chemical reactions were demonstrated with the example of the prebiotic Urey–Miller experiment. (31−33) As the configuration space can become very large, comprising multiple copies of all chemical species involved in the reaction, computational costs of carrying out first-principles calculations grow rapidly. This issue can be overcome by the application of a reactive classical force-field (for a recent review see ref (34)). (35,36) Unfortunately, apart from reduced accuracy, force-field parameters will, in general, not be available for any type of system which limits their applicability. Therefore, hybrid quantum-mechanical–molecular-mechanical approaches have been frequently applied to explore reaction pathways of complex systems with many degrees of freedom such as enzymatic reactions (for examples see refs (37−42) and reviews by Senn and Thiel (43−45)).
Naturally, MD simulations employing classical and ab initio force fields can be applied to sample conformational degrees of freedom. For systems featuring many degrees of freedom (e.g., proteins) enhanced sampling techniques such as local elevation (46) or metadynamics (47) are mandatory (see also refs (48) and (49)). Recent progress has been reviewed in refs (50−52). These approaches are among the most complex and time-consuming for conformational sampling. (53) Stochastic methods based on Monte Carlo (MC) simulated annealing are often faster than MD methods. (54−56) By sampling low-lying eigenmodes, they require less computational effort than MD simulations. Both MD and MC approaches are computationally too expensive for a high-throughput setting.
In 2013, Liu and co-workers proposed the stochastic surface walking (SSW) method for exploring PESs. (57) Their approach is based on bias-potential-driven dynamics and Metropolis MC sampling. Stationary points are perturbed toward a new configuration through randomly generated modes of displacement and the subsequent construction of a biasing potential. (57−60) For example, the SSW method was applied to predict the structure of complex fullerenes (58) and phase transitions (59) and to study the hydrolysis of epoxypropane and the decomposition of β-d-glucopyranose. (60)
Martínez-Núñez and co-workers developed an approach termed TS search using chemical dynamics simulations (TSSCDS), (61−65) in which high-energy dynamics employing semiempirical quantum chemical methods are performed to induce reactions to occur at high rates. Vibrational modes are populated to increase the rate at which TSs can be overcome. For large systems, due to their large number of vibrational modes, manual intervention is required to steer the simulation into directions of interest. The trajectory generated through the simulation is subsequently postprocessed, and bond-forming and bond-breaking events are identified. TS guesses are extracted from the trajectory and refined with semiempirical or density-functional methods. The TSSCDS method was successfully applied to reactions involving vinyl cyanide, formaldehyde, and formic acid and to the study of cobalt catalysis.
Usually, approximate TS candidates are then refined by utilizing Hessian information, i.e., second-order derivatives of the potential energy with respect to the nuclear coordinates. The Hessian of a TS guess structure is required to obtain the normal mode representing the reaction coordinate to follow. Eigenvector following (EVF) (66−72) is the most prominent example of such an approach, which will be reliable if the TS guess structure is close to the true TS. For large molecules, a full Hessian calculation will become computationally demanding or even unfeasible even if the Hessian is approximated. Therefore, several algorithms have been developed to circumvent the calculation of the full Hessian. A quasi-Newton–Raphson method was introduced by Broyden, (73) in which an approximate Hessian is built from gradients only and then updated by the gradients of intermediate points obtained during the optimization. Other approaches include schemes proposed by Munro and Wales (74) that avoid the full diagonalization of the Hessian, Lanczos subspace iteration methods, (75) and Davidson subspace iteration algorithms. (76−79)
Wheeler and co-workers developed a computational toolkit called AARON (An Automated Reaction Optimizer for New catalysts) (134−137) that constructs initial TS structures by mapping key atoms of new catalysts onto the positions of the corresponding atoms in previously computed TS structures based on a model catalyst. AARON then executes a protocol of computations consisting of constrained and unconstrained optimizations to yield optimized TS structures. AARON was successfully applied to bidentate Lewis-base catalyzed allylation and propargylation reactions.
3. Class 2: Structure Hopping by Chemical Heuristics
Click to copy section linkSection link copied!
Exploration strategies solely based on curvature information on one PES are often unsuitable for large chemical systems with many degrees of freedom and for reactive systems that require many PESs for their description owing to multiple steps with incoming reactants and outgoing side products. Starting from a minimum structure, it can be more effective to apply heuristics to rapidly identify potential products, and subsequently, search for a MEP connecting them. If two end points of an elementary reaction are known, interpolation methods (see, e.g., ref (80)) and string methods (78,81−91) can be applied to locate the MEP connecting them.
Conceptual knowledge of chemistry can be exploited to rapidly identify potential candidates for intermediates connected to the starting structure through an elementary reaction, in particular, if the type of reaction mechanism relevant to the reactive system under study is known. For example, from reaction databases or chemical heuristics, transformation rules can be formulated and applied to graph representations of the reacting molecules. These rules originate from concepts of bond order and valence and are therefore best suited for organic chemistry. In 1994, Broadbelt and co-workers pioneered this approach by introducing a method called Netgen. (92) The three-dimensional arrangement of atoms in molecules is transformed into a graph structure in which atoms and bonds are represented by nodes and edges, respectively. This gives rise to adjacency matrices that can be manipulated by matrix operations representing chemical transformations. (93,94) With the derived adjacency matrices, new three-dimensional arrangements of atoms are generated. Through repeated application of these transformation rules, new molecules are added to the list of intermediates involved in the global mechanism. In Broadbelt’s original work, elementary steps were not identified, and hence, activation barriers needed to be estimated with the Evans–Polanyi principle. (95)
In a similar spirit, Green and co-workers developed a software package called Reaction Mechanism Generator (RMG). (96,97) Many steps were taken to overcome challenges demonstrated by the approach of Broadbelt. In particular, kinetic parameters were estimated employing quantum chemical calculations to discard products that are likely to be reachable only by overcoming TSs featuring high activation barriers. RMG was employed to map, in an automated fashion, the mechanisms of the pyrolysis of methane (96) and n-butanol (98) and the steam cracking of n-hexane. (99) In addition, the Green and West groups successfully applied RMG to a variety of complex systems. (99−106) Similar to Netgen, RMG is ultimately limited by the application of concepts of bond order and valence.
Green and co-workers developed an approach in which graph transformations and path refinement algorithms are combined to find reaction pathways. (106,107) Very recently, they explored the reaction network of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, (106) by applying the Berny algorithm (108−110) coupled with the freezing string method, (88) single- and double-ended growing string methods, and the AFIR method.
Recently, Kim and co-workers utilized chemical heuristics to rapidly search for reaction pathways. (117) Through the application of molecular graph and reaction network analyses, they explored a so-called minimal reaction network consisting of intermediates that can be reached from the starting structures within a fixed number of bond dissociation and formation reactions. The minimal network is subjected to quantum chemical calculations to determine the kinetically most favorable reaction pathway. They applied this ansatz to recover the accepted mechanisms of the Claisen ester condensation and of cobalt-catalyzed hydroformylation reactions. (117)
The ZStruct approach developed by Zimmerman utilizes connectivity graphs to identify potential intermediates that are reachable when connections are formed or broken. (118,119) Intermediates are then subjected to a double-ended MEP search with the growing string method. (90,120−122) A limitation of ZStruct is the requirement that two reactants need to be aligned so that the reactive complex is close to a MEP. As a result, this approach is best suited for intramolecular reactions. (16) In addition, if two intermediates are connected by two elementary reactions, ZStruct will struggle to find a TS. Despite its shortcomings, ZStruct uncovered an unexpected side-reaction that was hampering a Ni-based C–H functionalization catalyst. (123) Furthermore, several other (catalytic) reactions have been studied with ZStruct. (124−126) Recently, Dewyer and Zimmerman addressed the limitations of ZStruct and developed ZStruct2. (127) In ZStruct2, reactants are prealigned to sample so-called driving coordinates that describe the expected elementary reactions. ZStruct2 was successfully applied to study transition metal catalysts. (128−131)
In Habershon’s approach, (132,133) connectivity graphs describe intermediates. Reaction pathways are examined by dynamics simulations over a Hamiltonian that can be updated to suit a change in the connectivity graph. The trajectories are processed and unique pathways are refined. Compared to the approach developed by Green and co-workers, Habershon’s method explores the potential energy surface more extensively, at the cost of running dynamics simulations.
West and co-workers demonstrated a novel approach to predict TS structures with a group-additive method. (111) Distances between reactive atoms at the TS are estimated with molecular group values so that an approximate TS can be constructed by distance geometry (DG)—a stochastic method that will be discussed below. The estimated TS structures are then optimized with standard electronic structure methods.
Aspuru-Guzik and co-workers developed a methodology based on formal bond orders (112−114) to model prebiotic reactions. (115) Instead of specifically encoding elementary reactions, transformation rules were based on a concept popular in organic chemistry, commonly denoted as arrow pushing, (116) and activation barriers were estimated (in ref (112) by employing Hammond’s postulate).
While being computationally efficient, graph-based descriptors rely on the concept of valence, which may perform well for many organic molecules but may fail for systems containing species with complex electronic structures such as transition-metal clusters. Furthermore, to ensure an exhaustive exploration with such an approach, completeness of the set of transformation rules is required. However, for an arbitrary, unknown chemical system this cannot be guaranteed. One will then be restricted to known chemical transformations, which may hamper the discovery of new chemical processes. We, therefore, pursued a more general approach based on first-principles heuristics that is applicable to any molecular system, also those containing transition metals. The general applicability of our approach is due to the fact that all heuristic rules are derived from the electronic wave function that is agnostic with respect to the composition of a molecule.
In order to explore a PES, we start from high-energy structures related to elementary reaction steps. For this purpose, molecular structures of reactive complexes are generated according to rules derived from conceptual electronic-structure theory. (138−140) Subsequently, they are optimized by quantum-chemical methods to produce stable intermediates of an emerging reaction network. (141) Pairs of intermediates in this network that might be related by an elementary reaction according to some structural similarity measure are then detected in an automated fashion and subjected to an automated search for the connecting TS. Compared to the other approaches, ours does not rely on the concept of chemical bonds and valence. In contrast, reactive sites are detected by relying on reactivity measures calculated from the electronic wave function. This protocol has been implemented in a software called Chemoton (named after a theory for the functioning of living systems proposed by Gánti (142)). We demonstrated the capabilities of our approach with the example of synthetic nitrogen fixation with the Yandulov–Schrock complex (143,144) where we were able to identify thousands of protonated structures leading to side and decomposition reactions that explain the catalyst’s low turnover number. (79) We also studied a prebiotic reaction to elucidate different pathways of early sugar formation (115,145,146) through the construction of a reaction network of unprecedented size. (147)
Our approach possesses additional salient features incorporated to make quantum chemical explorations a peer to experimental kinetic studies. To fight the combinatorial explosion of structures, we have combined the exploration with explicit kinetic modeling (148) in order to avoid wasting computational resources on regions of configuration space that are kinetically not accessible under reaction conditions (in our original implementation (141) we already applied simple energy cutoffs for this purpose). For specific exploration problems (e.g., those that are of purely organo-chemical nature), we can exploit fast semiempirical models, for which we implemented a stand-alone program that offers energies and gradients for all major models. (149) However, we also developed a universal semiempirical approach that can even deal with transition-metal complexes as it exploits the computational benefits of the neglect of diatomic differential overlap approximation by on-the-fly parametrization to more accurate calculations reference calculations that are then reliable for sequences of similar structures. (150) Most important in this endeavor to exploit fast (and hence, less accurate) methods to the largest extent is the possibility to assign errors to approximate electronic structure and physicochemical models (151−153) in such a way that a seamless uncertainty quantification is possible from the first-principles level to the rate constants and concentration fluxes of kinetic modeling. (154) We demonstrated that fast semiempirical and also density-functional methods can be calibrated in an exploration by comparison to ab initio reference data obtained for structures determined in an automated fashion on the fly. (155) For this purpose, we exploited confidence intervals of machine learning approaches (demonstrated at the example of Gaussian process regression). (155) It is important to note that we did not parametrize a machine learning model (which is likely to require too much data in order to be sufficiently reliable), but instead, we only exploited the feature of such models that error estimates become available.
Finally, we again need to address the problem of conformational flexibility, which opens up many routes across a PES to arrive from one compound at another one. There exist several efficient approaches for the exploration of conformers that are related to this second class of exploration strategies. DG methods stochastically generate sets of atomic coordinates that are refined against a set of interatomic distance constraints. Generated conformers are usually optimized with a molecular mechanics force field or with quantum-chemical methods to afford a candidate conformer. Implementations of DG can be found in DG-AMMOS (156) and RDKit. (157)
To reduce the conformational space that needs to be explored, the so-called rigid-rotor approximation is often introduced, (18) in which bond lengths and bond angles are kept fixed so that only torsional degrees of freedom are sampled. Genetic algorithms are a prominent class of methods for stochastic sampling of vast torsion-angle spaces as implemented in Balloon_GA, (158) but MC algorithms have also been used for stochastic sampling of torsional angles. (159,160) A general problem with stochastic methods is the possibility of missing relevant (i.e., accessible) conformers. As a result, the amount of sampling required is not known. Systematic conformer generation methods, which rely explicitly on the rigid-rotor approximation, attempt to enumerate all possible torsional degrees of freedom of a molecule. However, systematic enumeration of all possible torsion angles based on a starting conformation in a brute-force fashion will result in a combinatorial explosion of candidate conformers. Rule-based conformation generators limit the conformational space they explore. These rules are usually derived from analyses of torsional angles in solid-state structures found in databases such as the Protein Database (161) or the Cambridge Structural Database. (162,163)
We note that the generation of conformers for transition-state structures appears to be a hardly tackled problem despite its importance for subsequent kinetic modeling. Although one may generate (or sample) conformations of some transition-state structure with the methods discussed, this could lead to different transition-state structures upon optimization. It is then not obvious how to properly incorporate this set of structures into an absolute rate theory calculation for an elementary step from one compound to another. This becomes particularly difficult for conformational freedom in the solvent surrounding a reactive system at the transition state.
4. Class 3: Interactive Steering
Click to copy section linkSection link copied!
Human chemical intuition and computer simulations can form a closed feedback loop to efficiently explore particular regions of interest on a PES. This approach does not require the formulation of heuristic transformation rules but is based on human insight and local slope information. Interactive scientific computing very early addressed different human senses. The first steps toward combining computer simulations and the sense of touch were conceived in the early 1970s. (164−166) These conceptual studies explored how touch communication with computers may enhance human–machine symbiosis. Wilson and co-workers anticipated that interactivity and the possibility to feel simulations could be beneficial in the field of chemistry to better understand molecular structure and molecular interactions. (166) Since these early days, interactive immersion into a virtual molecular world has been considered as an intruiging approach for research and teaching. (167,168) However, a viral spreading has not yet occurred (169) because new designs of hardware devices for human-machine interaction in virtual and mixed realities are still under continuous development. It may be anticipated that the situation changes in the future when commodity devices become easily and cheaply available, as they are required for increasingly popular computer games.
Interactivity can be achieved by run-time modification of simulation parameters or by manipulation of atoms or molecules in the simulated system. Immersion may often facilitate and enable interaction, and accordingly, much effort has been devoted to designing frameworks that are as immersive as possible, often requiring specialized hardware. Immersion implies visual feedback and may be complemented by haptic (tactile) feedback. On the one hand, visual feedback is often realized by a three-dimensional representation of the simulated molecular system on a (computer) screen. More advanced setups are achieved through virtual reality or augmented reality, involving theater environments such as the cave automatic virtual environment (CAVE) (170) or head-mounted displays (HMDs). (171,172) Interactive simulations are generally steered with commodity computer mouses, three-dimensional mouses, sensors that track and record movement, or hand controllers. On the other hand, haptic feedback is achieved with devices combining three-dimensional positional input and force feedback. In chemistry-related applications, such devices allow for selection of atoms or molecules, move them in space, and provide a force feedback resulting from the manipulation. Some devices consider not only three dimensions for the positional degrees of freedom but also three dimensions for the rotation of the manipulated object. How to achieve realistic haptic feedback in a molecular context has been studied intensively and often depends on the targeted field of application. (173−180) While smooth visual immersion in virtual environments usually requires an update rate of 60 Hz, (181) the tactile sense is more sensitive and requires a 10- to 20-times increased refresh rate of about 1 kHz. (182,183) In addition to visual and haptic feedback, some applications also address the auditory sense, (170,184−187) and clearly voice control as an input aid could also be advantageous to enhance interactivity and immersion by reducing latency during input and structure modification.
4.1. Interactive Approaches in Classical Simulations
As interactivity requires fast physical property calculations (e.g., energies and forces), molecular mechanics approaches, i.e., Newtonian mechanics with hard-wired force fields, were the first target in molecular simulations because physical quantities are easy to evaluate. A prominent example is molecular docking. The high number of possibilities for binding sites between receptors and ligands, and the challenges of implementing automated algorithms for determining them motivated interactive approaches to take advantage of the human ability to locate reasonable candidates. The project GROPE (188,189) targeted the study of interacting proteins based on electrostatic and van der Waals interactions and allowed operators to manipulate molecules with a six-dimensional haptic device to explore the interaction between receptors and ligands. In 1997, interactive molecular docking was combined with genetic algorithms in the Stalk system in a CAVE environment. (190) It offered the possibility to not only visualize the genetic algorithm search in virtual reality but also suspend it and move the ligand to continue the search from another conformation. While a demonstration of a clear advantage of interactivity over traditional computational protocols requires extensive user studies, (189,191,192) the usefulness of haptic feedback for molecular docking was claimed in later studies along with algorithmic and technical improvements. (176,185,193−203) However, we note that especially haptic pointer devices are not completely convincing in docking studies because of (i) the weak van der Waals interactions that hardly allow one to feel an attraction between host and guest until one hits the repulsive wall of the r–12 terms and (ii) the huge number of such weak contacts that can hardly be properly addressed with a low-dimensional input/output device.
In the 1990s, steered molecular dynamics (204) (SMD) was developed to introduce artificial forces during molecular dynamics simulations. This allowed for computational studies of atomic force microscopy experiments and it was soon applied to the study of rare events. (205−208) A driving force was also Jarzynski’s theorem (209) that relates work performed on a system out of equilibrium to the free energy difference of the start and end points in equilibrium (although this would require a slowly acting force and extensive sampling of the complementary degrees of freedom). Moreover, the artificial forces in SMD are defined in advance and cannot be altered during the simulation. The wish to do so at runtime was one motivation behind interactive molecular dynamics. (210−212) First approaches consisted in changing simulation parameters intermittently or in adding user-specified forces through a graphical user interface. (172,213,214) With increasing computational power the interactive simulations have become increasingly immersive, and applications soon emerged in CAVE environments (184) or with specialized hardware such as HMDs (171,172) or haptic devices. (215,216) Recent years have seen continuous efforts to design new frameworks for interactive molecular dynamics in virtual reality (192,217−219) and to achieve a broader applicability of interactive molecular dynamics with commodity hardware. (186,220) Also, interactive molecular dynamics was recently combined with quantum chemical methods executed on graphics processing units. (221) Such interactive ab initio MD, however, suffered from convergence problems of iterative orbital optimization cycles that eventually break the immersion (see below for further discussion of such issues).
Another important application of interactive approaches in computational chemistry has been the generation and manipulation of chemical structures, which is often considered a preparatory step for a subsequent traditional calculation because of the approximate nature of the fast method that enables interactivity. In 1994, Brooks and co-workers introduced Sculpt, a modeling system for the manipulation of small proteins with continuous energy minimization. (222) Sculpt constrained bond length and bond angles but continuously minimized the potential energy due to torsion angles, hydrogen bonds, van der Waals and electrostatic interactions. Sculpt allowed operators to manipulate proteins with the computer mouse and could achieve an update rate of 11 Hz for a 20-residue protein. To ease the setup of large molecular structures, molecule editors allow for fast (real-time) structure optimization with classical force fields or very approximate noniterative semiempirical methods as implemented in Avogadro (223) and SAMSON, (224,225) respectively. Within the SAMSON environment, Redon and co-workers applied adaptive dynamics to enable interactive modeling of larger proteins (226) and hydrocarbon systems. (227) They also relied on a continuous energy minimization and allowed for changes to the molecular structure (atom addition and deletion) in addition to its manipulation. (227) They recognized the limits of nonreactive force fields and also studied the application of semiempirical quantum chemical methods (225,228) and extended the universal force field to support changes in the molecular topology. (229)
Different approaches emerged to allow for visualization of molecular structures or molecular dynamics simulations in virtual environments, (230−233) sometimes along with functionality for the edition and manipulation of molecules. (234−236) In 2000, Harvey and Gingold explored the electron density of atomic orbitals with haptic devices. (237) Comai and Mazza developed a similar tool to sense the electrostatic field resulting from quantum chemical calculations. (238) Satoh et al. designed a framework for studying the van der Waals interaction of noble gases described by a classical force field with haptic feedback. (239) Haptic devices were later used for the interactive exploration of the solvent accessible surface of proteins. (240) Different studies demonstrated the possible benefits of immersive and interactive approaches in education, (241−244) and multiple virtual reality frameworks were designed for simultaneous immersion of multiple persons, allowing for collaborative environments. (192,245−249)
4.2. Interactivity for Quantum Mechanical Calculations
Traditionally, quantum chemical studies have been prohibitively expensive to allow for interactivity. This is due to the mathematical structure of quantum mechanical equations, which involve expensive calculations of huge numbers of integrals and iterative solution procedures (in contrast to the straightforward and fast evaluation of an analytical formula for the energy and force derived from a classical force field). For this reason, quantum mechanical approaches have long been considered to be not amenable to interactive approaches (see, however, the next section).
To determine electronic energies and other properties, quantum chemical calculations require, as all computational modeling approaches, three steps shown in Figure 2a: the setup, the calculation, and the analysis of the results. For the setup, one generally creates a text-based input file containing the calculation settings and the specification of a molecular system. The calculation step commonly takes place on central processing units (CPUs) or cores thereof. Quantum chemical calculations typically require computation times of a few minutes up to a few weeks. To analyze the results, one then parses the values of interest from the generated output files. It is known to every practitioner of computational quantum chemistry that the computation time is the most time-consuming step. In light of the effort required for the actual calculation, setup and analysis times appear negligible.
Figure 2
Figure 2. Schematic course of a typical quantum chemical calculation. (a) Traditionally, the most time-intensive step is the computation step on the CPU. (b) With increasing CPU power, the duration of quantum chemical calculations decreases for a fixed system size and some given electronic structure model. (c) For a quasi-instantaneous calculation, the most time-intensive step is now no longer the computation itself, but the bottleneck becomes the setup and the analysis of the results.
An observation commonly known as Moore’s Law states that the number of transistors on a chip roughly doubles every two years. For quantum chemistry, this development has been highly beneficial (and has not come to end due to the growing number of cores of a CPU and the parallelism now inherent to all quantum chemistry software). On the one hand, it has allowed for studying larger molecular systems with increasing accuracy. On the other hand, if the size of the studied system or the algorithm’s accuracy is not increased, the calculation time will decrease over the years benefiting from more efficient hardware that becomes available, as illustrated in Figure 2b. With continuously increasing CPU power, calculation times can be greatly reduced up to the point where calculations become near-instantaneous. In such a situation, the traditional approach (setup, calculation, analysis) is dominated by the setup and analysis, not by the calculation itself, as depicted in Figure 2c. Furthermore, for near-instantaneous calculations setup and analysis are no longer separated in time.
In a traditional approach, the setup and analysis steps do not benefit from the increasing computing power. While for time-consuming calculations the time and human effort required for setup and analysis are negligible compared to the calculation itself, this is not the case for near-instantaneous calculations. To be able to fully benefit from near-instantaneous calculations, one must get rid of the text-based setup and analysis in the traditional sense altogether and consider fully interactive approaches to reactivity studies instead. Note that even most of the advanced molecule editors do not alleviate this problem as they help setting up inputs and inspecting results, but in general not to the degree that this (i) is quasi-instantaneous and (ii) can cope with a never-ending data influx of new results for continuously manipulated molecular structures. By contrast, true interactivity in quantum mechanical calculations opens new fields of research that combine the strengths of computers and human skills for making unprejudiced discoveries in molecular reactivity (by contrast to hard-wired classical force fields) as we shall discuss now.
When considering chemical reactivity studies, we note that this naturally requires a physical modeling based on elementary particles and hence on quantum mechanics. Only the well-known electromagnetic interaction operators of electrons and atomic nuclei allow us to quantify the emerging interaction energies of atoms and fragments in arbitrary configurations of molecular systems encountered in exploration studies of chemical reaction space. First interactive approaches for the study of chemical reactivity appeared in the past decade. They considered the interactive exploration of the PES based on the first-principles of quantum mechanics to determine reaction mechanisms and therefore require the application of quantum chemical methods. In 2009, we proposed haptic quantum chemistry (HQC) as a framework to explore the potential energy surface with a haptic device in which the force acts a descriptor for slope and, to a certain degree, also curvature. (250) The haptic force feedback first relied on an interpolation scheme that started from precalculated ab initio electronic-energy data points in configuration space. The algorithms underlying HQC were later improved and extended for a more automated and flexible workflow. (251) Afterward, our original HQC implementation was modified to no longer rely on interpolation, but rather on on-the-fly single-point calculations. (252) This new approach required a real-time quantum chemistry (RTQC) framework, which was shown to be feasible for small molecular systems within a density functional theory model or for those consisting of about 100 atoms within semiempirical models. (253) A first implementation within the SAMSON molecule editor (224) with advanced state-of-the-art semiempirical methods demonstrated the applicability and usefulness of RTQC. (254) The main components of a RTQC framework are illustrated in Figure 3.
Figure 3
Figure 3. Main components of a real-time quantum chemistry framework. The central element is the molecular structure under study (center) that is displayed (top right) to the operator. The operator can move atoms and experience the effects of his manipulations with a computer mouse or a haptic device (top left). Single-point calculations run continuously in the background (bottom) and deliver the nuclear forces underlying the reactivity exploration as well as other relevant quantum chemical properties.
The major issue for interactivity of quantum chemical calculations is that the single-point energy calculations require self-consistent field (SCF) iterations. This iterative procedure creates difficulties that are already present in standard quantum chemical calculations but become particularly troublesome in interactive approaches. First, one cannot predict a priori how much time will be required for a single-point calculation, especially for fast and drastic structure modifications introduced by the operator. Since the execution time is linked to the number of SCF iterations, this creates a strong incentive to reduce this number, which can be achieved by improving initial electronic densities of the SCF cycle. Second, there will be cases in which the SCF procedure simply does not converge or requires a large number of iterations. A nonconverging calculation results in an interruption of the flow of properties delivered to the interactive simulation, hence destroying immersion into the virtual molecular world. Third, there may be different solutions to the SCF equations, resulting in different electronic densities and quantum chemical properties. In an interactive setting, convergence to an incorrect SCF solution may then lead to a biased description of the molecular system under study.
In the past years, we developed approaches that addressed all of these issues and eventually allowed us to apply SCF-based electronic structure methods in interactive quantum mechanical settings for reaction mechanism exploration. It is important to understand that all of these developments, which we will discuss in the remainder of this section, address the two challenges of (i) efficiency leading to faster calculations and (ii) stability ensuring reliable results. Whereas both required convincing solutions in an interactive setting where the large frequency of results delivered (on a 100 ms to 1s rate) simply does not allow for inspecting possibly faulty results (and therefore they must be avoided or cured at all cost), we emphasize that they also become important for automated black-box algorithms discussed in classes 1 and 2 above, where, due to the sheer amount of data produced, a manual check of reliability becomes impossible (and therefore the calculations must not fail).
To address the first issue, we accelerated self-consistent field calculations by a density propagation algorithm for sequences of (similar) structures. (255) This strategy is related to other extrapolation approaches applied in ab initio molecular dynamics. (256,257) It delivers improved initial density matrices for single-point calculations and, hence, reduces the number of iterations required for convergence.
Considering the second challenge, it is mandatory that visual and haptic feedback should also be available in the case of calculations converging slowly or not at all. In order to guarantee reliable real-time feedback, we introduced a mediator strategy. (258) The mediator creates surrogate potentials that approximate the potential energy surface and enable high-frequency feedback. In addition, the mediator restricts the reactivity exploration to regions of configuration space for which the available orbitals are reliable until new data becomes eventually available.
As for the third difficulty, incorrectly converged calculations are often ignored or go undetected even in noninteractive reactivity studies. To ensure that interactive explorations rely on correctly converged quantum chemical calculations, we proposed a scheme that can quickly be evaluated (as required in a RTQC framework) and which perturbs the orbitals through random mixing in such a way that incorrect self-consistent field convergence is detected and cured. (259) This scheme continuously tests in the background whether lower-energy solutions can be obtained with randomly perturbed initial electronic densities.
In addition to making reactivity studies more intuitive, interactive quantum chemistry promotes novel approaches toward the way quantum chemical investigations are carried out. Most importantly, the exploration need not be limited to a specific, predefined PES with fixed charge and spin state. Since the quantum chemical calculations are fast, other states and properties can be calculated in the background in an automated fashion for the structures explored to notify the operator when important facts about reactivity may otherwise go undetected. For this scenario, we introduced the concept of molecular propensity with which multiple states of a molecular system are explored simultaneously. (260) It offers chemists the possibility to discover the inclination of a reactive system to undergo (unexpected) transformations such as reduction, oxidation, spin crossover, photoexcitation, or protonation.
For interactive exploration of reactivity, it is imperative to keep track of the structures and reactions seen during interactive explorations. For this, the raw exploration data must be processed to determine stable molecular structures as well as the reactions connecting them in the form of a reaction network. This can be achieved by converting sequences of structures recorded during an exploration to B-spline curves, from which we extract candidates for stable structures and elementary reactions. (261) The candidates are then optimized and stored in a reaction network. Note that this network of structures can be the same database as for the algorithms of classes 1 and 2, therefore facilitating synergies between all classes in an integrated fashion. To accomplish the stable optimization of reaction pathways and transition states in an automated fashion, we developed a new double-ended method called ReaDuct that describes reaction pathways by parametrized curves. (91) To determine minimum energy pathways and transition states, it optimizes the parameters of the curve rather than discrete structures along the reaction path.
5. Conclusions and Outlook
Click to copy section linkSection link copied!
In this work, we reviewed different approaches developed for the effective and efficient exploration of complex chemical reaction. While approaches exploiting local curvature information on the PES are highly systematic, they can be limited by computational cost, and it is difficult to steer such an exploration to regions of a PES that are truly relevant (for a given set of reactants and reaction conditions). By contrast, approaches utilizing some sort of heuristics may accelerate the exploration by employing graph-based transformation rules or concepts from quantum mechanics to efficiently discover potential intermediates. As a result, explorations across PESs become feasible. When heuristics are based on information directly extracted from the electronic wave function, such heuristics can be formulated so that they are universally applicable to systems containing molecules from the whole periodic table of the elements.
Interactive approaches allow the user to guide the system of interest through the configuration space, and thus, effectively explore particular regions that the user deems relevant to the chemical system under consideration. However, since this type of exploration is not systematic, critical reaction pathways may remain undiscovered. For interactivity and immersion into the molecular world, ultrafast single-point calculations are necessary. While such calculations are, in principle, feasible with methods of density-functional theory (DFT), (221,252) real-time quantum chemistry frameworks have so far relied on semiempirical approaches, (253) which are also advantageous and in actual use in algorithms from classes 1 and 2 (recall, however, our comments on reliability and error estimation in the section devoted to class 2).
We emphasize that none of the approaches in classes 1–3 can guarantee that all important elementary steps of some reaction network are actually found during an exploration process. However, they all represent much better options than a cumbersome and limited manual inspection, providing much more detail than the latter. It remains a challenge to strike the right balance between thoroughness and computational tractability. In Figure 4, the strengths of the different classes are summarized in a Venn diagram. Through the combination of the strengths of all three classes a truly reliable and universally applicable exploration protocol can be formulated. In our laboratory, a software package called SCINE (262) is currently being developed in which these three approaches are fully interoperable.
Figure 4
Figure 4. Combined strengths of three classes of exploration strategies result in a universally applicable exploration protocol.
Author Information
Click to copy section linkSection link copied!
- Markus Reiher - Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland;
http://orcid.org/0000-0002-9508-1565;
Biographies
Click to copy section linkSection link copied!
Gregor N. Simm
Gregor N. Simm was born and raised in Erlangen (Germany). He completed his BSc. and MSc. at ETH Zurich in Interdisciplinary Sciences. In 2014, he conducted his master’s thesis in the group of Alán Aspuru-Guzik at Harvard University, where he studied machine learning techniques to accelerate the discovery of new organic photovoltaic materials. From 2015 to 2018, he was working as a Ph.D. student under the supervision of Markus Reiher supported by a fellowship of the Fund of the German Chemical Industry. He developed approaches for the exploration of complex chemical reaction networks with error estimation capabilities. Since the fall of 2018, he has been working as a postdoctoral fellow in the Machine Learning Group at the University of Cambridge supported by an Early Postdoc.Mobility fellowship of the Swiss National Science Foundation.
Alain C. Vaucher
Alain C. Vaucher was born in Switzerland in 1990. After BSc and MSc degrees in Chemistry at ETH Zurich, he was a Ph.D. student in the group of Markus Reiher, where his research concentrated on interactive approaches for quantum chemistry. For his Ph.D. thesis he was awarded the IBM Research Prize 2018. During his time at ETH Zurich, he developed a strong interest for scientific computing and new technologies. His research is currently devoted to applications of artificial intelligence in chemistry.
Markus Reiher
Markus Reiher was born in East-Westphalia in 1971. He received his Ph.D. in theoretical chemistry from the University of Bielefeld working with Juergen Hinze in 1998 and spent time as a docent and professor at the Universities of Erlangen, Bonn, and Jena. Since 2006, he has been professor for theoretical chemistry at ETH Zurich. His research focuses on relativistic quantum chemistry, theoretical spectroscopy, electron correlation methods, density functional theory, reaction mechanisms, uncertainty quantification, interactive quantum mechanics, coordination chemistry, and quantum computing.
Acknowledgments
Click to copy section linkSection link copied!
This work was financially supported by the Schweizerischer Nationalfonds.
References
Click to copy section linkSection link copied!
This article references 262 other publications.
- 1Masters, C. Homogeneous Transition-Metal Catalysis: A Gentle Art, 1st ed.; Springer, 2011.Google ScholarThere is no corresponding record for this reference.
- 2Vinu, R.; Broadbelt, L. J. Unraveling Reaction Pathways and Specifying Reaction Kinetics for Complex Systems. Annu. Rev. Chem. Biomol. Eng. 2012, 3, 29– 54, DOI: 10.1146/annurev-chembioeng-062011-081108Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1GmtbnK&md5=c4ba8d6755e934d6a78993f8e67a6b85Unraveling reaction pathways and specifying reaction kinetics for complex systemsVinu, R.; Broadbelt, Linda J.Annual Review of Chemical and Biomolecular Engineering (2012), 3 (), 29-54CODEN: ARCBCY; ISSN:1947-5438. (Annual Reviews Inc.)A review. Many natural and industrial processes involve a complex set of competing reactions that include several different species. Detailed kinetic modeling of such systems can shed light on the important pathways involved in various transformations and therefore can be used to optimize the process conditions for the desired product compn. and properties. This review focuses on elucidating the various components involved in modeling the kinetics of pyrolysis and oxidn. of polymers. The elementary free radical steps that constitute the chain reaction mechanism of gas-phase/nonpolar liq.-phase processes are outlined. Specification of the rate coeffs. of the various reaction families, which is central to the theme of kinetics, is described. Construction of the reaction network on the basis of the types of end groups and reactive moieties in a polymer chain is discussed. Modeling frameworks based on the method of moments and kinetic Monte Carlo are evaluated using illustrations. Finally, the prospects and challenges in modeling biomass conversion are addressed.
- 3Ross, J. Determination of Complex Reaction Mechanisms. Analysis of Chemical, Biological and Genetic Networks. J. Phys. Chem. A 2008, 112, 2134– 2143, DOI: 10.1021/jp711313eGoogle ScholarThere is no corresponding record for this reference.
- 4Jorgensen, W. L. The Many Roles of Computation in Drug Discovery. Science 2004, 303, 1813– 1818, DOI: 10.1126/science.1096361Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXitFehu7w%253D&md5=77b2fac63e750ca7cdc7e4f35654549aThe Many Roles of Computation in Drug DiscoveryJorgensen, William L.Science (Washington, DC, United States) (2004), 303 (5665), 1813-1818CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. An overview is given on the diverse uses of computational chem. in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for detg. protein-ligand binding.
- 5Valdez, C. E.; Morgenstern, A.; Eberhart, M. E.; Alexandrova, A. N. Predictive Methods for Computational Metalloenzyme Redesign – a Test Case with Carboxypeptidase A. Phys. Chem. Chem. Phys. 2016, 18, 31744– 31756, DOI: 10.1039/C6CP02247BGoogle Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFCrsbbO&md5=b11bfcb0cc2fec4149ad6f9fc28ffa66Predictive methods for computational metalloenzyme redesign - a test case with carboxypeptidase AValdez, Crystal E.; Morgenstern, Amanda; Eberhart, Mark E.; Alexandrova, Anastassia N.Physical Chemistry Chemical Physics (2016), 18 (46), 31744-31756CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Computational metalloenzyme design is a multi-scale problem. It requires treating the metal coordination quantum mech., extensive sampling of the protein backbone, and addnl. accounting for the polarization of the active site by both the metal cation and the surrounding protein (a phenomenon called electrostatic preorganization). We bring together a combination of theor. methods that jointly offer these desired qualities: QM/DMD for mixed quantum-classical dynamic sampling, quantum theory of atoms in mols. (QTAIM) for the assessment of electrostatic preorganization, and D. Functional Theory (DFT) for mechanistic studies. Within this suite of principally different methods, there are both complementarity of capabilities and cross-validation. Using these methods, predictions can be made regarding the relative activities of related enzymes, as we show on the native Zn2+-dependent carboxypeptidase A (CPA), and its mutant proteins, which are hypothesized to hydrolyze modified substrates. For the native CPA, we replicated the catalytic mechanism and the rate in close agreement with the expt., giving validity to the QM/DMD predicted structure, the DFT mechanism, and the QTAIM assessment of catalytic activity. For most sequences of the modified substrate and tried CPA mutants, substantially worsened activity is predicted. However, for the substrate mutant that contains Asp instead of Phe at the C-terminus, one CPA mutant exhibits a reasonable activity, as predicted across the theor. methods. CPA is a well-studied system, and here it serves as a testing ground for the offered methods.
- 6Honkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Nørskov, J. K. Ammonia Synthesis from First-Principles Calculations. Science 2005, 307, 555– 558Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslOjuw%253D%253D&md5=4c6066f84d200c9c587b6dd1dcd3b0bfAmmonia Synthesis from First-Principles CalculationsHonkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Norskov, J. K.Science (Washington, DC, United States) (2005), 307 (5709), 555-558CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The rate of ammonia synthesis over a nanoparticle ruthenium catalyst can be calcd. directly on the basis of a quantum chem. treatment of the problem using d. functional theory. We compared the results to measured rates over a ruthenium catalyst supported on magnesium aluminum spinel. When the size distribution of ruthenium particles measured by transmission electron microscopy was used as the link between the catalyst material and the theor. treatment, the calcd. rate was within a factor of 3 to 20 of the exptl. rate. This offers hope for computer-based methods in the search for catalysts.
- 7Medford, A. J.; Wellendorff, J.; Vojvodic, A.; Studt, F.; Abild-Pedersen, F.; Jacobsen, K. W.; Bligaard, T.; Nørskov, J. K. Assessing the Reliability of Calculated Catalytic Ammonia Synthesis Rates. Science 2014, 345, 197– 200, DOI: 10.1126/science.1253486Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWjtLvK&md5=af3416666eeec422dd8f7c7543b9488eAssessing the reliability of calculated catalytic ammonia synthesis ratesMedford, Andrew J.; Wellendorff, Jess; Vojvodic, Aleksandra; Studt, Felix; Abild-Pedersen, Frank; Jacobsen, Karsten W.; Bligaard, Thomas; Norskov, Jens K.Science (Washington, DC, United States) (2014), 345 (6193), 197-200CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)We introduce a general method for estg. the uncertainty in calcd. materials properties based on d. functional theory calcns. We illustrate the approach for a calcn. of the catalytic rate of ammonia synthesis over a range of transition-metal catalysts. The correlation between errors in d. functional theory calcns. is shown to play an important role in reducing the predicted error on calcd. rates. Uncertainties depend strongly on reaction conditions and catalyst material, and the relative rates between different catalysts are considerably better described than the abs. rates. We introduce an approach for incorporating uncertainty when searching for improved catalysts by evaluating the probability that a given catalyst is better than a known std.
- 8Matera, S.; Maestri, M.; Cuoci, A.; Reuter, K. Predictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid Dynamics. ACS Catal. 2014, 4, 4081– 4092, DOI: 10.1021/cs501154eGoogle Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12kurjF&md5=e0f052a4546ccf857b9e898b8d08825bPredictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid DynamicsMatera, Sebastian; Maestri, Matteo; Cuoci, Alberto; Reuter, KarstenACS Catalysis (2014), 4 (11), 4081-4092CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)We present a numerical framework to integrate first-principles kinetic Monte Carlo (1p-kMC) based microkinetic models into the powerful computational fluid dynamics (CFD) package CatalyticFoam. This allows for the simultaneous account of a predictive-quality surface reaction kinetics inside an explicitly described catalytic reactor geometry. Crucial means toward an efficient and stable implementation are the exploitation of the disparate time scales of surface chem. and gas-phase transport, as well as the reliable interpolation of irregularly gridded 1p-kMC data by means of an error-based modified Shepard approach. We illustrate the capabilities of the framework using the CO oxidn. at Pd(100) and RuO2(110) model catalysts in different reactor configurations and fluid dynamic conditions as showcases. These showcases underscore both the necessity and value of having reliable treatments of the surface chem. and flow inside integrated multiscale catalysis simulations when aiming at an at.-scale understanding of the catalytic function in near-ambient environments. Our examples highlight how intricately this function is affected by specifics of the reactor geometry and heat dissipation channels on the one end, and on the other end by characteristics of the intrinsic catalytic activity that are only captured by treatments beyond prevalent mean-field rate equations.
- 9Reuter, K. Ab Initio Thermodynamics and First-Principles Microkinetics for Surface Catalysis. Catal. Lett. 2016, 146, 541– 563, DOI: 10.1007/s10562-015-1684-3Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xps1CnsQ%253D%253D&md5=352bd644b8fabaf14fc7e70d0f29b5a0Ab Initio Thermodynamics and First-Principles Microkinetics for Surface CatalysisReuter, KarstenCatalysis Letters (2016), 146 (3), 541-563CODEN: CALEER; ISSN:1011-372X. (Springer)A review; ab initio thermodn. and first-principles microkinetic simulations have become std. tools in research on model catalysts. Complementing dedicated in situ expts. these techniques contribute to our evolving mechanistic understanding, in particular of a reaction-induced dynamical evolution of the working catalyst surface. This topical review surveys the methodol. foundations and ongoing developments of both techniques, and specifically illustrates the type of insights they provide in the context of in situ model catalyst studies. This insight points at substantial deviations from the std. picture that analyzes catalytic function merely in terms of properties of and processes at active sites as they emerge from a crystal lattice truncation of the nominal catalyst bulk material.
- 10Baxter, E. T.; Ha, M.-A.; Cass, A. C.; Alexandrova, A. N.; Anderson, S. L. Ethylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst Morphologies. ACS Catal. 2017, 7, 3322– 3335, DOI: 10.1021/acscatal.7b00409Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVSqsbc%253D&md5=d1944c4c7de19d6e44ea69ac739c458dEthylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst MorphologiesBaxter, Eric T.; Ha, Mai-Anh; Cass, Ashley C.; Alexandrova, Anastassia N.; Anderson, Scott L.ACS Catalysis (2017), 7 (5), 3322-3335CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Catalytic dehydrogenation of ethylene on size-selected Ptn (n = 4, 7, 8) clusters deposited on the surface of Al2O3 was studied exptl. and theor. Clusters were mass-selected, deposited on the alumina support, and probed by a combination of low energy ion scattering, temp.-programmed desorption and reaction of C2D4 and D2, XPS, d. functional theory, and statistical mech. theory. Pt7 is identified as the most catalytically active cluster, while Pt4 and Pt8 exhibit comparable activities. The higher activity can be related to the cluster structure and particularly to the distribution of cluster morphologies accessible at the temps. and coverage with ethylene in catalytic conditions. Specifically, while Pt7 and Pt8 on alumina have very similar prismatic global min. geometries, Pt7 at higher temps. also has access to single-layer isomers, which become more and more predominant in the cluster catalyst ensemble upon increasing ethylene coverage. Single-layer isomers feature greater charge transfer from the support and more binding sites that activate ethylene for dehydrogenation rather than hydrogenation or desorption. Size-dependent susceptibility to coking and deactivation was also studied. Results show that size-dependent catalytic activity of clusters is not a simple property of single cluster geometry but the av. over a statistical ensemble at relevant conditions.
- 11Ha, M.-A.; Baxter, E. T.; Cass, A. C.; Anderson, S. L.; Alexandrova, A. N. Boron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3. J. Am. Chem. Soc. 2017, 139, 11568– 11575, DOI: 10.1021/jacs.7b05894Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1GjsbrO&md5=c4fb4ca3671fed66af60f96ac51a86cbBoron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3Ha, Mai-Anh; Baxter, Eric T.; Cass, Ashley C.; Anderson, Scott L.; Alexandrova, Anastassia N.Journal of the American Chemical Society (2017), 139 (33), 11568-11575CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Size-selected supported clusters of transition metals can be remarkable and highly tunable catalysts. A particular example is Pt clusters deposited on alumina, which have been shown to dehydrogenate hydrocarbons in a size-specific manner. Pt7, of the three sizes studied, is the most active and, therefore, like many other catalysts, deactivates by coking during reactions in hydrocarbon-rich environments. Using a combination of expt. and theory, we show that nanoalloying Pt7 with boron modifies the alkene-binding affinity to reduce coking. From a fundamental perspective, the comparison of exptl. and theor. results shows the importance of considering not simply the most stable cluster isomer, but rather the ensemble of accessible structures as it changes in response to temp. and reagent coverage.
- 12Ulissi, Z. W.; Medford, A. J.; Bligaard, T.; Nørskov, J. K. To Address Surface Reaction Network Complexity Using Scaling Relations Machine Learning and DFT Calculations. Nat. Commun. 2017, 8, 14621, DOI: 10.1038/ncomms14621Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czjtFamuw%253D%253D&md5=bde19b4dcb6abce90b2ea7ab073e1c6eTo address surface reaction network complexity using scaling relations machine learning and DFT calculationsUlissi Zachary W; Norskov Jens K; Medford Andrew J; Bligaard ThomasNature communications (2017), 8 (), 14621 ISSN:.Surface reaction networks involving hydrocarbons exhibit enormous complexity with thousands of species and reactions for all but the very simplest of chemistries. We present a framework for optimization under uncertainty for heterogeneous catalysis reaction networks using surrogate models that are trained on the fly. The surrogate model is constructed by teaching a Gaussian process adsorption energies based on group additivity fingerprints, combined with transition-state scaling relations and a simple classifier for determining the rate-limiting step. The surrogate model is iteratively used to predict the most important reaction step to be calculated explicitly with computationally demanding electronic structure theory. Applying these methods to the reaction of syngas on rhodium(111), we identify the most likely reaction mechanism. Propagating uncertainty throughout this process yields the likelihood that the final mechanism is complete given measurements on only a subset of the entire network and uncertainty in the underlying density functional theory calculations.
- 13Vereecken, L.; Glowacki, D. R.; Pilling, M. J. Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and Applications. Chem. Rev. 2015, 115, 4063– 4114, DOI: 10.1021/cr500488pGoogle Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmtVWqs7s%253D&md5=75c3bde1b210e3c1555d0c946f8e4976Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and ApplicationsVereecken, Luc; Glowacki, David R.; Pilling, Michael J.Chemical Reviews (Washington, DC, United States) (2015), 115 (10), 4063-4114CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review is presented. Chem. Kinetics in Tropospheric Chem. is studied.
- 14Ludlow, R. F.; Otto, S. Systems Chemistry. Chem. Soc. Rev. 2008, 37, 101– 108, DOI: 10.1039/B611921MGoogle Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVWhtQ%253D%253D&md5=151c83f30396538fccc0ea2f9c016d26Systems chemistryLudlow, R. Frederick; Otto, SijbrenChemical Society Reviews (2008), 37 (1), 101-108CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A tutorial review. The study of complex mixts. of interacting synthetic mols. has historically not received much attention from chemists, even though research into complexity is well established in the neighboring fields. However, with the huge recent interest in systems biol. and the availability of modern anal. techniques this situation is likely to change. In this tutorial review we discuss some of the incentives for developing systems chem. and we highlight the pioneering work in which mol. networks are making a splash. A distinction is made between networks under thermodn. and kinetic control. The former include dynamic combinatorial libraries while the latter involve pseudo-dynamic combinatorial libraries, oscillating reactions and networks of autocatalytic and replicating compds. These studies provide fundamental insights into the organizational principles of mol. networks and how these give rise to emergent properties such as amplification and feedback loops, and may eventually shed light on the origin of life. The knowledge obtained from the study of mol. networks should ultimately enable us to engineer new systems with properties and functions unlike any conventional materials.
- 15Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: Oxford, 2001.Google ScholarThere is no corresponding record for this reference.
- 16Dewyer, A. L.; Argüelles, A. J.; Zimmerman, P. M. Methods for Exploring Reaction Space in Molecular Systems. WIREs Comput. Mol. Sci. 2018, 8, e1354 DOI: 10.1002/wcms.1354Google ScholarThere is no corresponding record for this reference.
- 17Sameera, W. M. C.; Maeda, S.; Morokuma, K. Computational Catalysis Using the Artificial Force Induced Reaction Method. Acc. Chem. Res. 2016, 49, 763– 773, DOI: 10.1021/acs.accounts.6b00023Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvFSnsb0%253D&md5=761857a94f5b7c7366b98650d8a42646Computational Catalysis Using the Artificial Force Induced Reaction MethodSameera, W. M. C.; Maeda, Satoshi; Morokuma, KeijiAccounts of Chemical Research (2016), 49 (4), 763-773CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)The artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy is an automatic approach to explore all important reaction paths of complex reactions. Most traditional methods in computational catalysis require guess reaction paths. On the other hand, the AFIR approach locates local min. (LMs) and transition states (TSs) of reaction paths without a guess, and therefore finds unanticipated as well as anticipated reaction paths. The AFIR method has been applied for multicomponent org. reactions, such as the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer catalysis. In the presence of several reactants, many equil. structures are possible, leading to a no. of reaction pathways. The AFIR method in the GRRM strategy dets. all of the important equil. structures and subsequent reaction paths systematically. As the AFIR search is fully automatic, exhaustive trial-and-error and guess-and-check processes by the user can be eliminated. At the same time, the AFIR search is systematic, and therefore a more accurate and comprehensive description of the reaction mechanism can be detd.The AFIR method has been used for the study of full catalytic cycles and reaction steps in transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron-catalyzed carbon-carbon bond formation reactions in aq. media. Some AFIR applications have targeted the selectivity-detg. step of transition-metal-catalyzed asym. reactions, including stereoselective water-tolerant lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of establishing the selectivity of a reaction, systematic sampling of the transition states is crit. In this direction, AFIR is very useful for performing a systematic and automatic detn. of TSs. In the presence of a comprehensive description of the transition states, the selectivity of the reaction can be calcd. more accurately.For relatively large mol. systems, the computational cost of AFIR searches can be reduced by using the ONIOM(QM:QM) or ONIOM(QM:MM) methods. In common practice, d. functional theory (DFT) with a relatively small basis set is used for the high-level calcn., while a semiempirical approach or a force field description is used for the low-level calcn. After approx. LMs and TSs are detd., std. computational methods (e.g., DFT with a large basis set) are used for the full mol. system to det. the true LMs and TSs and to rationalize the reaction mechanism and selectivity of the catalytic reaction.The examples in this Account evidence that the AFIR method is a powerful approach for accurate prediction of the reaction mechanisms and selectivities of complex catalytic reactions. Therefore, the AFIR approach in the GRRM strategy is very useful for computational catalysis.
- 18Hawkins, P. C. D. Conformation Generation: The State of the Art. J. Chem. Inf. Model. 2017, 57, 1747– 1756, DOI: 10.1021/acs.jcim.7b00221Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFagu7bE&md5=776818e66798d1987e015440a28e208eConformation Generation: The State of the ArtHawkins, Paul C. D.Journal of Chemical Information and Modeling (2017), 57 (8), 1747-1756CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The generation of conformations for small mols. is a problem of continuing interest in cheminformatics and computational drug discovery. This review will present an overview of methods used to sample conformational space, focusing on those methods designed for org. mols. commonly of interest in drug discovery. Different approaches to both the sampling of conformational space and the scoring of conformational stability will be compared and contrasted, with an emphasis on those methods suitable for conformer sampling of large nos. of drug-like mols. Particular attention will be devoted to the appropriate utilization of information from exptl. solid-state structures in validating and evaluating the performance of these tools. The review will conclude with some areas worthy of further investigation.
- 19Ohno, K.; Maeda, S. A Scaled Hypersphere Search Method for the Topography of Reaction Pathways on the Potential Energy Surface. Chem. Phys. Lett. 2004, 384, 277– 282, DOI: 10.1016/j.cplett.2003.12.030Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXksFWguw%253D%253D&md5=d695800fcf7c758ae9e5f6213d187edaA scaled hypersphere search method for the topography of reaction pathways on the potential energy surfaceOhno, Koichi; Maeda, SatoshiChemical Physics Letters (2004), 384 (4-6), 277-282CODEN: CHPLBC; ISSN:0009-2614. (Elsevier Science B.V.)An algorithm for finding pathways to transition states (TS) or dissocn. channels (DC) from equil. structures (EQ) on the potential energy surface (PES) is presented. The pathways around an EQ can be discovered at min. on the scaled hypersphere which would have a const. energy when the potentials are harmonic. Topog. maps including all TS, DC, and EQ were obtained for ab initio PES of H2O and HCHO in the MP2/3-21G level. The present scaled hypersphere search technique in combination with a downhill-walk algorithm enables us to make a topog. anal. of the PES for a given chem. compn.
- 20Maeda, S.; Ohno, K. Ab Initio Studies on Synthetic Routes of Glycine from Simple Molecules via Ammonolysis of Acetolactone: Applications of the Scaled Hypersphere Search Method. Chem. Lett. 2004, 33, 1372– 1373, DOI: 10.1246/cl.2004.1372Google ScholarThere is no corresponding record for this reference.
- 21Maeda, S.; Ohno, K. Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to Ab Initio Surfaces of Formaldehyde and Propyne Molecules. J. Phys. Chem. A 2005, 109, 5742– 5753, DOI: 10.1021/jp0513162Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksl2mtLk%253D&md5=68d94d344ec0774f5313ba93e456ffe3Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to ab Initio Surfaces of Formaldehyde and Propyne MoleculesMaeda, Satoshi; Ohno, KoichiJournal of Physical Chemistry A (2005), 109 (25), 5742-5753CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Tech. details of a new global mapping technique for finding equil. (EQ) and transition structures (TS) on potential energy surfaces (PES), the scaled hypersphere search (SHS) method (Ohno, K.; Maeda, S. Chem. Phys. Lett. 2004, 384, 277), are presented. On the basis of a simple principle that reaction pathways are found as anharmonic downward distortions of PES around an EQ point, the reaction pathways can be obtained as energy min. on the scaled hypersphere surface, which would have a const. energy when the potentials are harmonic. Connections of SHS paths between each EQ are very similar to corresponding intrinsic reaction coordinate (IRC) connections. The energy max. along the SHS path reaches a region in close proximity to the TS of the reaction pathway, and the subsequent geometry optimization from the SHS max. structure easily converges to the TS. The SHS method, using the one-after-another algorithm connecting EQ and TS, considerably reduces the multidimensional space to be searched to certain limited regions around the pathways connecting each EQ with the neighboring TS. Applications of the SHS method have been made to ab initio surfaces of formaldehyde and propyne mols. to obtain systematically five EQ and nine TS for formaldehyde and seven EQ and 32 TS for propyne.
- 22Ohno, K.; Maeda, S. Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted Analogues. J. Phys. Chem. A 2006, 110, 8933– 8941, DOI: 10.1021/jp061149lGoogle Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlvVWlsLk%253D&md5=b057c5984bdd877c2a57f80cfe6aa8a6Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted AnaloguesOhno, Koichi; Maeda, SatoshiJournal of Physical Chemistry A (2006), 110 (28), 8933-8941CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Global reaction route mapping of equil. structures, transition structures, and their connections on potential energy surface (PES) has been done for MCHO (M = H, Li, Na, Al, Cu) and HCO2M (M = H, Li). A one-after-another technique based on the scaled hypersphere search method has been successfully applied to exploring unknown chem. structures, transition structures, and reaction pathways for organometallic systems. Upon metal substitution, considerable changes of stable structures, reaction pathways, and relative heights of transition structures have been discovered, though some features are similar among the analogs. Al and Cu atoms were found to behave as very strong scissors to cut the CO double bond in MCHO. Energy profiles of the CO insertion into Li-H and Li-CH3 bonds were found to be very similar, esp. around the structures where the Li atom is not directly connected with the Me group, which indicates little effects of alkyl substitution on the reaction route topol.
- 23Maeda, S.; Ohno, K.; Morokuma, K. Systematic Exploration of the Mechanism of Chemical Reactions: The Global Reaction Route Mapping (GRRM) Strategy Using the ADDF and AFIR Methods. Phys. Chem. Chem. Phys. 2013, 15, 3683– 3701, DOI: 10.1039/c3cp44063jGoogle Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXislynsrg%253D&md5=3091bebd5edabab18bdabe51eb001e65Systematic exploration of the mechanism of chemical reactions: the global reaction route mapping (GRRM) strategy using the ADDF and AFIR methodsMaeda, Satoshi; Ohno, Koichi; Morokuma, KeijiPhysical Chemistry Chemical Physics (2013), 15 (11), 3683-3701CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Global reaction route mapping (GRRM), a fully-automated search for all important reaction pathways relevant to a given purpose, from quantum chem. calcns. enables systematic elucidation of complex chem. reaction mechanisms. However, GRRM had previously been limited to very simple systems. This is mainly because such calcns. are highly demanding even in small systems when a brute-force sampling is considered. Hence, the authors have developed two independent but complementary methods: anharmonic downward distortion following (ADDF) and artificial force induced reaction (AFIR) methods. ADDF can follow reaction pathways starting from local min. on the potential energy surface (PES) toward transition structures (TSs) and dissocn. channels. AFIR can find pathways starting from two or more reactants toward TSs for their associative reactions. ADDF searches for A X type isomerization and A X + Y type dissocn. pathways, whereas AFIR finds A + B X (+ Y) type associative pathways. Both follow special paths called the ADDF path and the AFIR path, and these tend to pass through near TSs of corresponding reaction pathways, giving approx. TSs. Such approx. TSs can easily be reoptimized to corresponding true TSs by std. geometry optimizations. From these two methods, the authors proposed practical strategies of GRRM. The GRRM strategies were applied to a variety of chem. systems ranging from thermal- and photochem.-reactions in small systems to organometallic- and enzyme-catalysis, from quantum chem. calcns. In this perspective, the authors present an overview of the GRRM strategies and some results of applications. Their practical usage for systematic prediction is also discussed.
- 24Satoh, H.; Oda, T.; Nakakoji, K.; Uno, T.; Tanaka, H.; Iwata, S.; Ohno, K. Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers. J. Chem. Theory Comput. 2016, 12, 5293– 5308, DOI: 10.1021/acs.jctc.6b00439Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFOktr%252FF&md5=a395292cdbf67ed58b06748344d48939Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of D-Glucose ConformersSatoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, KoichiJournal of Chemical Theory and Computation (2016), 12 (11), 5293-5308CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)This paper describes approach that is built upon the potential energy surface (PES)-based conformational anal. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search was achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the min. and TS structures by simply taking into account the math. feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equil. (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalcn. anal. of the deduced r-map is interactively carried out using the RMapViewer software the authors have developed. This paper presents computational details of the PES-based conformational anal. and its application to D-glucose. The calcns. were performed for an isolated glucose mol. in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-D-glucose is composed of 201 Equiv and 435 TS conformers and that for β-D-glucose is composed of 202 Equiv and 371 TS conformers. For the postcalcn. anal. of the conformational r-maps by using the RMapViewer software program the authors found multiple min. energy paths (MEPs) between global min. of 1C4 and 4C1 chair conformations. The anal. using RMapViewer allows us to confirm the thermodn. and kinetic predominance of 4C1 conformations; i.e., the potential energy of the global min. of 4C1 is lower than that of 1C4 (thermodn. predominance) and that the highest energy of those of all the TS structures along a route from 4C1 to 1C4 is lower than that of 1C4 to 4C1 (kinetic predominance).
- 25Maeda, S.; Morokuma, K. A Systematic Method for Locating Transition Structures of A+B→X Type Reactions. J. Chem. Phys. 2010, 132, 241102, DOI: 10.1063/1.3457903Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvFShtLs%253D&md5=9260f723c31e0b78b5677bb4a89f21d7Communications: A systematic method for locating transition structures of A + B → X type reactionsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Physics (2010), 132 (24), 241102/1-241102/4CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Search for transition structures (TSs) as first-order saddles is one of the most important tasks in theor. study of chem. reaction. Although automated search has been established either by starting from a local min. (MIN) or by connecting two MINs, there is no systematic method which can locate TSs of A + B → X (+ Y) type reactions starting from sepd. reactants. We propose such an approach for the first time; it was demonstrated to work very well in the SN2, Diels-Alder, and Wittig reactions. (c) 2010 American Institute of Physics.
- 26Maeda, S.; Morokuma, K. Finding Reaction Pathways of Type A+B→X: Toward Systematic Prediction of Reaction Mechanisms. J. Chem. Theory Comput. 2011, 7, 2335– 2345, DOI: 10.1021/ct200290mGoogle Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXosVCktro%253D&md5=85e666d25ec4858a5150bae96893f52aFinding Reaction Pathways of Type A + B → X: Toward Systematic Prediction of Reaction MechanismsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Theory and Computation (2011), 7 (8), 2335-2345CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In these five decades, many useful tools have been developed for exploring quantum chem. potential energy surfaces. The success in theor. studies of chem. reaction mechanisms has been greatly supported by these tools. However, systematic prediction of reaction mechanisms starting only from given reactants and catalysts is still very difficult. Toward this goal, we describe the artificial force induced reaction (AFIR) method for automatically finding reaction paths of type A + B → X (+ Y). By imposing an artificial force to given reactants and catalysts, the method can find the reactive sites very efficiently. Further pressing by the artificial force provides approx. transition states and product structures, which can be easily reoptimized to the corresponding true ones. This procedure can be executed very efficiently just by minimizing a single function called the AFIR function. All important reaction paths can be found by repeating this cycle starting from many initial orientations. We also discuss perspectives of automated reaction path search methods toward the above goal.
- 27Maeda, S.; Taketsugu, T.; Morokuma, K. Exploring Transition State Structures for Intramolecular Pathways by the Artificial Force Induced Reaction Method. J. Comput. Chem. 2014, 35, 166– 173, DOI: 10.1002/jcc.23481Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaqs77J&md5=18ee5becec9b21d0bdcef4d37b50a48dExploring transition state structures for intramolecular pathways by the artificial force induced reaction methodMaeda, Satoshi; Taketsugu, Tetsuya; Morokuma, KeijiJournal of Computational Chemistry (2014), 35 (2), 166-173CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Finding all required transition state (TS) structures is an important but hard task in theor. study of complex reaction mechanisms. An efficient automated TS search method, artificial force induced reaction (AFIR), was extended to intramol. reactions. The AFIR method was developed for intermol. associative pathways between two or more reactants. Although it also was applied to intramol. reactions by dividing mols. manually into fragments, the fragmentation scheme was not automated. The authors propose an automated fragmentation scheme. Using this fragmentation scheme and the AFIR method, a fully automated search algorithm for intramol. pathways is introduced. This version for intramol. reactions is called single-component AFIR (SC-AFIR), to distinguish it from multicomponent AFIR for intermol. reactions. SC-AFIR was tested with two reactions, the Claisen rearrangement and the first step of cobalt-catalyzed hydroformylation, and successfully located all important pathways reported in the literature. © 2013 Wiley Periodicals, Inc.
- 28Maeda, S.; Harabuchi, Y.; Takagi, M.; Taketsugu, T.; Morokuma, K. Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces. Chem. Rec. 2016, 16, 2232– 2248, DOI: 10.1002/tcr.201600043Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XptV2iurg%253D&md5=fb8514d68f9fefc53f4d5f9ad8e19e06Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy SurfacesMaeda, Satoshi; Harabuchi, Yu; Takagi, Makito; Taketsugu, Tetsuya; Morokuma, KeijiChemical Record (2016), 16 (5), 2232-2248CODEN: CRHEAK; ISSN:1528-0691. (Wiley-VCH Verlag GmbH & Co. KGaA)In this account, a tech. overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chem. reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimol. and multicomponent reactions and the latter to unimol. isomerization and dissocn. reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene mol. Finally, possible applications of the AFIR method are discussed.
- 29Yoshimura, T.; Maeda, S.; Taketsugu, T.; Sawamura, M.; Morokuma, K.; Mori, S. Exploring the Full Catalytic Cycle of Rhodium(I)–BINAP-Catalysed Isomerisation of Allylic Amines: A Graph Theory Approach for Path Optimisation. Chem. Sci. 2017, 8, 4475– 4488, DOI: 10.1039/C7SC00401JGoogle Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntlWgt7s%253D&md5=c2ab51df0053f782bc9e9f5323ec2358Exploring the full catalytic cycle of rhodium(I)-BINAP-catalysed isomerisation of allylic amines: a graph theory approach for path optimisationYoshimura, Takayoshi; Maeda, Satoshi; Taketsugu, Tetsuya; Sawamura, Masaya; Morokuma, Keiji; Mori, SeijiChemical Science (2017), 8 (6), 4475-4488CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)We explored the reaction mechanism of the cationic rhodium(I)-BINAP complex catalyzed isomerization of allylic amines using the artificial force induced reaction method with the global reaction route mapping strategy, which enabled us to search for various reaction paths without assumption of transition states. The entire reaction network was reproduced in the form of a graph, and reasonable paths were selected from the complicated network using Prim's algorithm. As a result, a new dissociative reaction mechanism was proposed. Our comprehensive reaction path search provided rationales for the E/Z and S/R selectivities of the stereoselective reaction.
- 30Puripat, M.; Ramozzi, R.; Hatanaka, M.; Parasuk, W.; Parasuk, V.; Morokuma, K. The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction. J. Org. Chem. 2015, 80, 6959– 6967, DOI: 10.1021/acs.joc.5b00407Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVans7nM&md5=7f6185df4c8e5c3802f013bc36a694c7The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent ReactionPuripat, Maneeporn; Ramozzi, Romain; Hatanaka, Miho; Parasuk, Waraporn; Parasuk, Vudhichai; Morokuma, KeijiJournal of Organic Chemistry (2015), 80 (14), 6959-6967CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The recently developed artificial force induced reaction (AFIR) method was applied to search systematically all possible multicomponent pathways for the Biginelli reaction mechanism. The most favorable pathway starts with the condensation of the urea and benzaldehyde, followed by the addn. of Et acetoacetate. Remarkably, a second urea mol. catalyzes nearly every step of the reaction. Thus, the Biginelli reaction is a urea-catalyzed multicomponent reaction. The reaction mechanism was found to be identical in both protic and aprotic solvents.
- 31Saitta, A. M.; Saija, F. Miller Experiments in Atomistic Computer Simulations. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 13768– 13773, DOI: 10.1073/pnas.1402894111Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSju7nN&md5=711514af5c0a3a8d6d0a226d29be2d8bMiller experiments in atomistic computer simulationsSaitta, Antonino Marco; Saija, FranzProceedings of the National Academy of Sciences of the United States of America (2014), 111 (38), 13768-13773CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The celebrated Miller expts. reported on the spontaneous formation of amino acids from a mixt. of simple mols. reacting under an elec. discharge, giving birth to the research field of prebiotic chem. However, the chem. reactions involved in those expts. have never been studied at the at. level. Here the authors report on, to the authors' knowledge, the first ab initio computer simulations of Miller-like expts. in the condensed phase. The authors' study, based on the recent method of treatment of aq. systems under elec. fields and on metadynamics anal. of chem. reactions, shows that glycine spontaneously forms from mixts. of simple mols. once an elec. field is switched on and identifies formic acid and formamide as key intermediate products of the early steps of the Miller reactions, and the crucible of formation of complex biol. mols.
- 32Wang, L.-P.; Titov, A.; McGibbon, R.; Liu, F.; Pande, V. S.; Martínez, T. J. Discovering Chemistry with an Ab Initio Nanoreactor. Nat. Chem. 2014, 6, 1044– 1048, DOI: 10.1038/nchem.2099Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVGitbnI&md5=201fe998c04f0c9b9a7aa6ebf329a2c5Discovering chemistry with an ab initio nanoreactorWang, Lee-Ping; Titov, Alexey; McGibbon, Robert; Liu, Fang; Pande, Vijay S.; Martinez, Todd J.Nature Chemistry (2014), 6 (12), 1044-1048CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)Chem. understanding is driven by the exptl. discovery of new compds. and reactivity, and is supported by theory and computation that provide detailed phys. insight. Although theor. and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodol. and computational advances harken the advent of their principal role in discovery. Here, we report the development and application of the ab initio nanoreactor-a highly accelerated first-principles mol. dynamics simulation of chem. reactions that discovers new mols. and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor, we show new pathways for glycine synthesis from primitive compds. proposed to exist on the early Earth, which provide new insight into the classic Urey-Miller expt. These results highlight the emergence of theor. and computational chem. as a tool for discovery, in addn. to its traditional role of interpreting exptl. findings.
- 33Wang, L.-P.; McGibbon, R. T.; Pande, V. S.; Martinez, T. J. Automated Discovery and Refinement of Reactive Molecular Dynamics Pathways. J. Chem. Theory Comput. 2016, 12, 638– 649, DOI: 10.1021/acs.jctc.5b00830Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVGku7nL&md5=6a731baa0767e0105247b156289fe8baAutomated Discovery and Refinement of Reactive Molecular Dynamics PathwaysWang, Lee-Ping; McGibbon, Robert T.; Pande, Vijay S.; Martinez, Todd J.Journal of Chemical Theory and Computation (2016), 12 (2), 638-649CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe a flexible and broadly applicable energy refinement method, "nebterpolation," for identifying and characterizing the reaction events in a mol. dynamics (MD) simulation. The new method is applicable to ab initio simulations with hundreds of atoms contg. complex and multimol. reaction events. A key aspect of nebterpolation is smoothing of the reactive MD trajectory in internal coordinates to initiate the search for the reaction path on the potential energy surface. We apply nebterpolation to analyze the reaction events in an ab initio nanoreactor simulation that discovers new mols. and mechanisms, including a C-C coupling pathway for glycolaldehyde synthesis. We find that the new method, which incorporates information from the MD trajectory that connects reactants with products, produces a dramatically distinct set of min. energy paths compared to existing approaches that start from information for the reaction end points alone. The energy refinement method described here represents a key component of an emerging simulation paradigm where mol. dynamics simulations are applied to discover the possible reaction mechanisms.
- 34Meuwly, M. Reactive Molecular Dynamics: From Small Molecules to Proteins. WIREs Comput. Mol. Sci. 2018, 0, e1386 DOI: 10.1002/wcms.1386Google ScholarThere is no corresponding record for this reference.
- 35van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A 2001, 105, 9396– 9409, DOI: 10.1021/jp004368uGoogle Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFChu78%253D&md5=ea59efc08d5e135745df988f2006a7fdReaxFF: A Reactive Force Field for Hydrocarbonsvan Duin, Adri C. T.; Dasgupta, Siddharth; Lorant, Francois; Goddard, William A., IIIJournal of Physical Chemistry A (2001), 105 (41), 9396-9409CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)To make practical the mol. dynamics simulation of large scale reactive chem. systems (1000 s of atoms), the authors developed ReaxFF, a force field for reactive systems. ReaxFF uses a general relation between bond distance and bond order on one hand and between bond order and bond energy however, that leads to proper dissocn. of bonds to sepd. atoms. Other valence terms present in the force field (angle and torsion) are defined in terms of the same bond orders so that all these terms go to zero smoothly as bonds break. In addn., ReaxFF has Coulomb and Morse (van der Waals) potentials to describe nonbond interactions between all atoms (no exclusions). These nonbond interactions are shielded at short range so that the Coulomb and van der Waals interactions become const. as Rij → 0. The authors report here the ReaxFF for hydrocarbons. The parameters were derived from quantum chem. calcns. on bond dissocn. and reactions of small mols. plus heat of formation and geometry data for a no. of stable hydrocarbon compds. The ReaxFF provides a good description of these data. Generally, the results are of an accuracy similar or better than PM3, while ReaxFF is ∼100 times faster. In turn, the PM3 is ∼100 times faster than the QC calcns. Thus, with ReaxFF the authors hope to be able to study complex reactions in hydrocarbons.
- 36Döntgen, M.; Przybylski-Freund, M.-D.; Kröger, L. C.; Kopp, W. A.; Ismail, A. E.; Leonhard, K. Automated Discovery of Reaction Pathways, Rate Constants, and Transition States Using Reactive Molecular Dynamics Simulations. J. Chem. Theory Comput. 2015, 11, 2517– 2524, DOI: 10.1021/acs.jctc.5b00201Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vjt1Gjtg%253D%253D&md5=7f936903e2258f886ccce3fc8fef0996Automated discovery of reaction pathways, rate constants, and transition states using reactive molecular dynamics simulationsDontgen Malte; Przybylski-Freund Marie-Dominique; Kroger Leif C; Kopp Wassja A; Ismail Ahmed E; Leonhard KaiJournal of chemical theory and computation (2015), 11 (6), 2517-24 ISSN:.We provide a methodology for deducing quantitative reaction models from reactive molecular dynamics simulations by identifying, quantifying, and evaluating elementary reactions of classical trajectories. Simulations of the inception stage of methane oxidation are used to demonstrate our methodology. The agreement of pathways and rates with available literature data reveals the potential of reactive molecular dynamics studies for developing quantitative reaction models.
- 37Fischer, S.; Karplus, M. Conjugate Peak Refinement: An Algorithm for Finding Reaction Paths and Accurate Transition States in Systems with Many Degrees of Freedom. Chem. Phys. Lett. 1992, 194, 252– 261, DOI: 10.1016/0009-2614(92)85543-JGoogle Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XltFSqtrk%253D&md5=938aae7d35f6942adbd76bf19c19cf9dConjugate peak refinement: an algorithm for finding reaction paths and accurate transition states in systems with many degrees of freedomFischer, Stefan; Karplus, MartinChemical Physics Letters (1992), 194 (3), 252-61CODEN: CHPLBC; ISSN:0009-2614.An algorithm is presented for detg. multidimensional reaction coordinates between two known conformers. Only the energy function and its gradient are required. The resulting paths follow the adiabatic energy valleys and have energy max. that are true saddle points, which can be multiple along each path. The method is suitable for the study of complex isomerization reactions, including allosteric transitions in proteins and more general conformational changes of macromols.
- 38Florián, J.; Goodman, M. F.; Warshel, A. Computer Simulation of the Chemical Catalysis of DNA Polymerases: Discriminating between Alternative Nucleotide Insertion Mechanisms for T7 DNA Polymerase. J. Am. Chem. Soc. 2003, 125, 8163– 8177, DOI: 10.1021/ja028997oGoogle Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXksFWgsbY%253D&md5=98029baf5458f072872a0746ea5ab990Computer simulation of the chemical catalysis of DNA polymerases: Discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymeraseFlorian, Jan; Goodman, Myron F.; Warshel, AriehJournal of the American Chemical Society (2003), 125 (27), 8163-8177CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Understanding the chem. step in the catalytic reaction of DNA polymerases is essential for elucidating the mol. basis of the fidelity of DNA replication. The present work evaluates the free energy surface for the nucleotide transfer reaction of T7 polymerase by free energy perturbation/empirical valence bond (FEP/EVB) calcns. A key aspect of the enzyme simulation is a comparison of enzymic free energy profiles with the corresponding ref. reactions in water using the same computational methodol., thereby enabling a quant. est. for the free energy of the nucleotide insertion reaction. The reaction is driven by the FEP/EVB methodol. between valence bond structures representing the reactant, pentacovalent intermediate, and the product states. This pathway corresponds to three microscopic chem. steps, deprotonation of the attacking group, a nucleophilic attack on the Pα atom of the dNTP substrate, and departure of the leaving group. Three different mechanisms for the first microscopic step, the generation of the RO- nucleophile from the 3'-OH hydroxyl of the primer, are examd.: (i) proton transfer to the bulk solvent, (ii) proton transfer to one of the ionic oxygens of the Pα phosphate group, and (iii) proton transfer to the ionized Asp 654 residue. The most favorable reaction mechanism in T7 pol is predicted to involve the proton transfer to Asp 654. This finding sheds light on the long standing issue of the actual role of conserved aspartates. The structural preorganization that helps to catalyze the reaction is also considered and analyzed. The overall calcd. mechanism consists of three subsequent steps with a similar activation free energy of about 12 kcal/mol. The similarity of the activation barriers of the three microscopic chem. steps indicates that the T7 polymerase may select against the incorrect dNTP substrate by raising any of these barriers. The relative height of these barriers comparing right and wrong dNTP substrates should therefore be a primary focus of future computational studies of the fidelity of DNA polymerases.
- 39Garcia-Viloca, M.; Gao, J.; Karplus, M.; Truhlar, D. G. How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. Science 2004, 303, 186– 195, DOI: 10.1126/science.1088172Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtlGhug%253D%253D&md5=35766752530af526c8bdc99774a8e9daHow enzymes work: Analysis by modern rate theory and computer simulationsGarcia-Viloca, Mireia; Gao, Jiali; Karplus, Martin; Truhlar, Donald G.Science (Washington, DC, United States) (2004), 303 (5655), 186-195CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review and discussion. Advances in transition state theory and computer simulations are providing new insights into the sources of enzyme catalysis. Both the lowering of the activation free energy and changes in the generalized transmission coeff. (recrossing of the transition state, tunneling, and nonequil. contributions) can play a role. A framework for understanding these effects is presented, and the contributions of the different factors, as illustrated by specific enzymes, are identified and quantified by computer simulations. The resulting understanding of enzyme catalysis is used to comment on alternative proposals of how enzymes work.
- 40Imhof, P.; Fischer, S.; Smith, J. C. Catalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical Analysis. Biochemistry 2009, 48, 9061– 9075, DOI: 10.1021/bi900585mGoogle Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtV2mtbvP&md5=88ce54a5f9131bc8ad11b1dbd07f8e6eCatalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical AnalysisImhof, Petra; Fischer, Stefan; Smith, Jeremy C.Biochemistry (2009), 48 (38), 9061-9075CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)Endonucleases, such as the restriction enzyme EcoRV, cleave the DNA backbone at a specific recognition sequence. We have investigated the catalytic mechanism of backbone phosphodiester hydrolysis by the restriction enzyme EcoRV by means of hybrid quantum mech./mol. mech. calcns. An exhaustive computation of different reaction pathways is performed, thus generating a network of pathways. Comparison of the computed (AM1d/MM) enzymic reaction pathways with an analogous mechanism for small-mol. model systems [AM1/d and B3LYP/6-31++G(d,p)] reveals that the transition barriers for associative hydrolysis, which is more probable in the model systems, are not lowered by the enzyme. Instead, a reaction mechanism which has mostly dissociative character is more likely. The protein environment is tuned to significantly electrostatically stabilize the transition state structures. The direct catalytic impact of essential residues is detd. The magnesium metal ion activates a water mol., thus facilitating protonation of the leaving group. A redn. of the coordination no. of the magnesium metal ion from six to four upon the positioning of the attacking water mol. explains why larger metal ions, such as calcium, are not catalytically active. The nucleophile is generated by the transfer of a proton from the attacking water mol. to a carboxylic oxygen atom of aspartate 90. The catalytic effect of lysine 92 involves proper positioning of the scissile phosphate group and, more importantly, stabilization of the metaphosphate intermediate in an orientation optimal for attack of the nucleophile.
- 41Reidelbach, M.; Betz, F.; Mäusle, R. M.; Imhof, P. Proton Transfer Pathways in an Aspartate-Water Cluster Sampled by a Network of Discrete States. Chem. Phys. Lett. 2016, 659, 169– 175, DOI: 10.1016/j.cplett.2016.07.021Google ScholarThere is no corresponding record for this reference.
- 42Imhof, P. A. Networks Approach to Modeling Enzymatic Reactions. Methods Enzymol. 2016, 578, 249– 271, DOI: 10.1016/bs.mie.2016.05.025Google ScholarThere is no corresponding record for this reference.
- 43Senn, H. M.; Thiel, W. QM/MM Methods for Biological Systems. Top. Curr. Chem. 2007, 268, 173– 290, DOI: 10.1007/128_2006_084Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvVOlt7c%253D&md5=bf5f07823db75b3e05018ed47b70d2c1QM/MM methods for biological systemsSenn, Hans Martin; Thiel, WalterTopics in Current Chemistry (2007), 268 (Atomistic Approaches in Modern Biology), 173-290CODEN: TPCCAQ; ISSN:0340-1022. (Springer GmbH)A review. Thirty years after the seminal contribution by Warshel and Levitt, we review the state of the art of combined quantum-mechanics/mol.-mechanics (QM/MM) methods, with a focus on biomol. systems. We provide a detailed overview of the methodol. of QM/MM calcns. and their use within optimization and simulation schemes. A tabular survey of recent applications, mostly to enzymic reactions, is given.
- 44Senn, H. M.; Thiel, W. QM/MM Studies of Enzymes. Curr. Opin. Chem. Biol. 2007, 11, 182– 187, DOI: 10.1016/j.cbpa.2007.01.684Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvFegurw%253D&md5=361cc5b164e23e5a71dac6f4bbf7d673QM/MM studies of enzymesSenn, Hans Martin; Thiel, WalterCurrent Opinion in Chemical Biology (2007), 11 (2), 182-187CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) methods are making rapid progress both methodol. and with respect to their range of application. Mechanistic studies on enzymes, including contributions toward the understanding of enzyme catalysis, continue to be a major target. They are joined by calcns. of pKa values, redox properties, ground- and excited-state spectroscopic parameters, and excited-state dynamics. Methodol. advances include improved QM/MM schemes, in particular new approaches for an effective treatment of the QM-MM electrostatic interactions, and the incorporation of new efficient and accurate QM methods in QM/MM schemes.
- 45Senn, H. M.; Thiel, W. QM/MM Methods for Biomolecular Systems. Angew. Chem., Int. Ed. 2009, 48, 1198– 1229, DOI: 10.1002/anie.200802019Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXitFOqs7g%253D&md5=c51da58b0525651c71f9c393a79023beQM/MM methods for biomolecular systemsSenn, Hans Martin; Thiel, WalterAngewandte Chemie, International Edition (2009), 48 (7), 1198-1229CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) approaches have become the method of choice for modeling reactions in biomol. systems. Quantum-mech. (QM) methods are required for describing chem. reactions and other electronic processes, such as charge transfer or electronic excitation. However, QM methods are restricted to systems of up to a few hundred atoms. However, the size and conformational complexity of biopolymers calls for methods capable of treating up to several 100,000 atoms and allowing for simulations over time scales of tens of nanoseconds. This is achieved by highly efficient, force-field-based mol. mechanics (MM) methods. Thus to model large biomols. the logical approach is to combine the two techniques and, to use a QM method for the chem. active region (e.g., substrates and co-factors in an enzymic reaction) and an MM treatment for the surroundings (e.g., protein and solvent). The resulting schemes are commonly referred to as combined or hybrid QM/MM methods. They enable the modeling of reactive biomol. systems at a reasonable computational effort while providing the necessary accuracy.
- 46Huber, T.; Torda, A. E.; van Gunsteren, W. F. Local Elevation: A Method for Improving the Searching Properties of Molecular Dynamics Simulation. J. Comput.-Aided Mol. Des. 1994, 8, 695– 708, DOI: 10.1007/BF00124016Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXjtVOnsrw%253D&md5=8d352c5753f9870081d4851ff12e58cdLocal elevation: a method for improving the searching properties of molecular dynamics simulationHuber, Thomas; Torda, Andrew E.; van Gunsteren, Wilfred F.Journal of Computer-Aided Molecular Design (1994), 8 (6), 695-708CODEN: JCADEQ; ISSN:0920-654X. (ESCOM)The concept of memory has been introduced into a mol. dynamics algorithm. This was done so as to persuade a mol. system to visit new areas of conformational space rather than be confined to a small no. of low-energy regions. The method is demonstrated on a simple model system and the 11-residue cyclic peptide cyclosporin A. For comparison, calcns. were also performed using simulated temp. annealing and a potential energy annealing scheme. Although the method can only be applied to systems with a small no. of degrees of freedom, it offers the chance to generate a multitude of different low-energy structures, where other methods only give a single one or few. This is clearly important in problems such as drug design, where one is interested in the conformational spread of a system.
- 47Laio, A.; Parrinello, M. Escaping Free-Energy Minima. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 12562– 12566, DOI: 10.1073/pnas.202427399Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XnvFGiurc%253D&md5=48d5bc7436f3ef9d78369671e70fa608Escaping free-energy minimaLaio, Alessandro; Parrinello, MicheleProceedings of the National Academy of Sciences of the United States of America (2002), 99 (20), 12562-12566CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We introduce a powerful method for exploring the properties of the multidimensional free energy surfaces (FESs) of complex many-body systems by means of coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates. A characteristic feature of these dynamics is the presence of a history-dependent potential term that, in time, fills the min. in the FES, allowing the efficient exploration and accurate detn. of the FES as a function of the collective coordinates. We demonstrate the usefulness of this approach in the case of the dissocn. of a NaCl mol. in water and in the study of the conformational changes of a dialanine in soln.
- 48Christen, M.; van Gunsteren, W. F. On Searching in, Sampling of, and Dynamically Moving through Conformational Space of Biomolecular Systems: A Review. J. Comput. Chem. 2008, 29, 157– 166, DOI: 10.1002/jcc.20725Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2sjktVOitQ%253D%253D&md5=c508200635d58b25f5ee678a9c016f87On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A reviewChristen Markus; van Gunsteren Wilfred FJournal of computational chemistry (2008), 29 (2), 157-66 ISSN:0192-8651.Methods to search for low-energy conformations, to generate a Boltzmann-weighted ensemble of configurations, or to generate classical-dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest.
- 49Bernardi, R. C.; Melo, M. C. R.; Schulten, K. Enhanced Sampling Techniques in Molecular Dynamics Simulations of Biological Systems. Biochim. Biophys. Acta, Gen. Subj. 2015, 1850, 872– 877, DOI: 10.1016/j.bbagen.2014.10.019Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVanurbN&md5=44e3ac1aa042c35ee08aa86a6a63e78eEnhanced sampling techniques in molecular dynamics simulations of biological systemsBernardi, Rafael C.; Melo, Marcelo C. R.; Schulten, KlausBiochimica et Biophysica Acta, General Subjects (2015), 1850 (5), 872-877CODEN: BBGSB3; ISSN:0304-4165. (Elsevier B.V.)A review. Mol. dynamics has emerged as an important research methodol. covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local min. sepd. by high-energy barriers, which govern the biomol. motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange mol. dynamics, metadynamics and simulated annealing. Here the authors present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biol. systems and the choice of a suitable method is connected to biol. and phys. characteristics of the system, in particular system size. While metadynamics and replica-exchange mol. dynamics are the most adopted sampling methods to study biomol. dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromol. complexes. Mol. dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biol. function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of mol. dynamics.
- 50Shim, J.; MacKerell, A. D., Jr. Computational Ligand-Based Rational Design: Role of Conformational Sampling and Force Fields in Model Development. MedChemComm 2011, 2, 356– 370, DOI: 10.1039/c1md00044fGoogle Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Kht7c%253D&md5=70d822d1ca2faa484f723fb109597b77Computational ligand-based rational design: role of conformational sampling and force fields in model developmentShim, Jihyun; MacKerell, Alexander D., Jr.MedChemComm (2011), 2 (5), 356-370CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)A review. A significant no. of drug discovery efforts are based on natural products or high throughput screens from which compds. showing potential therapeutic effects are identified without knowledge of the target mol. or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compd.'s structure and physicochem. attributes to its biol. activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compds. with improved biol. attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quant. structure-activity relationships (QSAR) yielding quant. ests. of activities based on physiochem. properties, and to similarity searching, which explores compds. with similar properties as well as various combinations of the above. A no. of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is mol. mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression anal. to neural networks, from which the SAR is detd. Accordingly, for effective application of LBDD for SAR detns. it is important that the compds. be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modeling is largely based on use of the appropriate empirical force field for the mols. being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations assocd. with empirical energy functions and conformational sampling methods.
- 51Ballard, A. J.; Martiniani, S.; Stevenson, J. D.; Somani, S.; Wales, D. J. Exploiting the Potential Energy Landscape to Sample Free Energy. WIREs Comput. Mol. Sci. 2015, 5, 273– 289, DOI: 10.1002/wcms.1217Google ScholarThere is no corresponding record for this reference.
- 52De Vivo, M.; Masetti, M.; Bottegoni, G.; Cavalli, A. Role of Molecular Dynamics and Related Methods in Drug Discovery. J. Med. Chem. 2016, 59, 4035– 4061, DOI: 10.1021/acs.jmedchem.5b01684Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlWksLs%253D&md5=b3d8a4fb5705a3555c2bb2a962420396Role of Molecular Dynamics and Related Methods in Drug DiscoveryDe Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, AndreaJournal of Medicinal Chemistry (2016), 59 (9), 4035-4061CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)Mol. dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate est. of the thermodn. and kinetics assocd. with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theor. background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water mols. in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.
- 53Tsujishita, H.; Hirono, S. Camdas: An Automated Conformational Analysis System Using Molecular Dynamics. J. Comput.-Aided Mol. Des. 1997, 11, 305– 315, DOI: 10.1023/A:1007964913898Google ScholarThere is no corresponding record for this reference.
- 54Wilson, S. R.; Cui, W.; Moskowitz, J. W.; Schmidt, K. E. Applications of Simulated Annealing to the Conformational Analysis of Flexible Molecules. J. Comput. Chem. 1991, 12, 342– 349, DOI: 10.1002/jcc.540120307Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXitVKhsLw%253D&md5=7ca487c05c358c760a76eed13145b5deApplications of simulated annealing to the conformational analysis of flexible moleculesWilson, Stephen R.; Cui, Weili; Moskowitz, Jules W.; Schmidt, Kevin E.Journal of Computational Chemistry (1991), 12 (3), 342-9CODEN: JCCHDD; ISSN:0192-8651.A soln. to the global min. problem which uses the simulated annealing algorithm of Kirkpatrick is described. This method is a Metropolis (e-ΔE/kT) Monte Carlo sampling of conformation space with simultaneous constraint of the search by lowering the temp. T so that the search converges on the global min. The Anneal-Conformer program has been extensively tested with peptides and org. mols. using either the Amber or MM2 force fields. A history file of the simulated annealing process allows reconstruction of the random walk in conformation space for subsequent examn. Thus plots of distance and dihedral angle changes during the search for the global min. can be examd. to deduce mol. shape and flexibility. A sep. program Conf-Gen reads the history file and exts. all low energy conformations visited during the run.
- 55Sperandio, O.; Souaille, M.; Delfaud, F.; Miteva, M. A.; Villoutreix, B. O. MED-3DMC: A New Tool to Generate 3D Conformation Ensembles of Small Molecules with a Monte Carlo Sampling of the Conformational Space. Eur. J. Med. Chem. 2009, 44, 1405– 1409, DOI: 10.1016/j.ejmech.2008.09.052Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjtVSjtLw%253D&md5=bc3b0f5ea5b23da6eec7048f39081448MED-3DMC: A new tool to generate 3D conformation ensembles of small molecules with a Monte Carlo sampling of the conformational spaceSperandio, Olivier; Souaille, Marc; Delfaud, Francois; Miteva, Maria A.; Villoutreix, Bruno O.European Journal of Medicinal Chemistry (2009), 44 (4), 1405-1409CODEN: EJMCA5; ISSN:0223-5234. (Elsevier Masson SAS)Obtaining an efficient sampling of the low to medium energy regions of a ligand conformational space is of primary importance for getting insight into relevant binding modes of drug candidates, or for the screening of rigid mol. entities on the basis of a predefined pharmacophore or for rigid body docking. Here, we report the development of a new computer tool that samples the conformational space by using the Metropolis Monte Carlo algorithm combined with the MMFF94 van der Waals energy term. The performances of the program have been assessed on 86 drug-like mols. that resulted from an ADME/tox profiling applied on cocrystalized small mols. and were compared with the program Omega on the same dataset. Our program has also been assessed on the 85 mols. of the Astex diverse set. Both test sets show convincing performance of our program at sampling the conformational space.
- 56Grebner, C.; Becker, J.; Stepanenko, S.; Engels, B. Efficiency of Tabu-Search-Based Conformational Search Algorithms. J. Comput. Chem. 2011, 32, 2245– 2253, DOI: 10.1002/jcc.21807Google ScholarThere is no corresponding record for this reference.
- 57Shang, C.; Liu, Z.-P. Stochastic Surface Walking Method for Structure Prediction and Pathway Searching. J. Chem. Theory Comput. 2013, 9, 1838– 1845, DOI: 10.1021/ct301010bGoogle Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOlt7c%253D&md5=ff2585b886e8cc63d4443934f5317048Stochastic Surface Walking Method for Structure Prediction and Pathway SearchingShang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (3), 1838-1845CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We propose an unbiased general-purpose potential energy surface (PES) searching method for both the structure and the pathway prediction of a complex system. The method is based on the idea of bias-potential-driven dynamics and Metropolis Monte Carlo. A central feature of the method is able to perturb smoothly a structural configuration toward a new configuration and simultaneously has the ability to surmount the high barrier in the path. We apply the method for locating the global min. (GM) of short-ranged Morse clusters up to 103 atoms starting from a random structure without using extra information from the system. In addn. to GM searching, the method can identify the pathways for chem. reactions with large dimensionality, as demonstrated in a nanohelix transformation contg. 222 degrees of freedoms.
- 58Zhang, X.-J.; Shang, C.; Liu, Z.-P. From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex Material. J. Chem. Theory Comput. 2013, 9, 3252– 3260, DOI: 10.1021/ct400238jGoogle Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXosVegsr0%253D&md5=0e94b080ff99b33134c703b183357f15From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex MaterialZhang, Xiao-Jie; Shang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (7), 3252-3260CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)It is of general concern whether the automated structure prediction of unknown material without recourse to any knowledge from expt. is ever possible considering the daunting complexity of potential energy surface (PES) of material. Here we demonstrate that the stochastic surface walking (SSW) method can be a general and promising soln. to this ultimate goal, which is applied to assemble carbon fullerenes contg. up to 100 atoms (including 60, 70, 76, 78, 80, 84, 90, 96, and 100 atoms) from randomly distributed atoms, a long-standing challenge in global optimization. Combining the SSW method with a parallel replica exchange algorithm, we can locate the global min. (GM) of these large fullerenes efficiently without being trapped in numerous energy-nearly degenerate isomers. Detailed analyses on the SSW trajectories allow us to rationalize how and why the SSW method is able to explore the highly complex PES, which highlights the abilities of SSW method for surmounting the high barrier and the preference of SSW trajectories to the low energy pathways. The work demonstrates that the parallel SSW method is a practical tool for predicting unknown materials.
- 59Shang, C.; Zhang, X.-J.; Liu, Z.-P. Stochastic Surface Walking Method for Crystal Structure and Phase Transition Pathway Prediction. Phys. Chem. Chem. Phys. 2014, 16, 17845– 17856, DOI: 10.1039/C4CP01485EGoogle Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyms7jE&md5=c5dc152fa492d8978d79bbcf35313753Stochastic surface walking method for crystal structure and phase transition pathway predictionShang, Cheng; Zhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2014), 16 (33), 17845-17856CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The detn. of crystal structures and the solid-to-solid phase transition mechanisms are two important and related subjects in material science. Here we develop an unbiased general-purpose potential energy surface (PES) searching method, namely, SSW-crystal method, for prediction of both the crystal structure and the crystal phase transition pathway. The SSW-crystal method features with stochastic surface walking (SSW) via repeated small structural perturbation by taking into account the second deriv. information on both the lattice and the atom degrees of freedom. The SSW-crystal method is capable of overcoming the high barrier of phase transition and identifying the desirable phase transition reaction coordinates. By applying the SSW-crystal method to a set of examples, including SiO2 crystal up to 162 atoms per cell, Lennard-Jones model crystals up to 256 atoms, ternary SrTiO3 crystal of 50 atoms and the rutile-to-anatase TiO2 phase transition, we show that the SSW-crystal method can efficiently locate the global min. (GM) from random initial structures without a priori knowledge of the system, and also allows for exhaustive sampling of the phase transition pathways, from which the lowest energy pathway can be obtained.
- 60Zhang, X.-J.; Liu, Z.-P. Reaction Sampling and Reactivity Prediction Using the Stochastic Surface Walking Method. Phys. Chem. Chem. Phys. 2015, 17, 2757– 2769, DOI: 10.1039/C4CP04456HGoogle Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVSgur3F&md5=c5ac6082903ea35d005a1e00ab73febeReaction sampling and reactivity prediction using the stochastic surface walking methodZhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2015), 17 (4), 2757-2769CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The prediction of chem. reactivity and thus the design of new reaction systems are the key challenges in chem. Here, we develop an unbiased general-purpose reaction sampling method, the stochastic surface walking based reaction sampling (SSW-RS) method, and show that the new method is a promising soln. for reactivity prediction of complex reaction systems. The SSW-RS method is capable of sampling both the configuration space of the reactant and the reaction space of pathways, owing to the combination of two recently developed theor. methods, namely, the stochastic surface walking (SSW) method for potential energy surface (PES) exploration and the double-ended surface walking (DESW) method for building pathways. By integrating with first principles calcns., we show that the SSW-RS method can be applied to investigate the kinetics of complex org. reactions featuring many possible reaction channels and complex hydrogen-bonding networks, as demonstrated here using two examples, epoxypropane hydrolysis in aq. soln. and β-D-glucopyranose decompn. Our results show that simultaneous sampling of the soft hydrogen-bonding conformations and the chem. reactions involving hard bond making/breaking can be achieved in the SSW-RS simulation, and the mechanism and kinetics can be predicted without a priori information on the system. Unexpected new chem. for these reactions is revealed and discussed. In particular, despite many possible pathways for β-D-glucopyranose decompn., the SSW-RS shows that only β-D-glucose and levoglucosan are kinetically preferred direct products and the 5- or 7-member ring products should be secondary products derived from β-D-glucose or levoglucosan. As a general tool for reactivity prediction, the SSW-RS opens a new route for the design of rational reactions.
- 61Vázquez, S. A.; Martínez-Núñez, E. HCN Elimination from Vinyl Cyanide: Product Energy Partitioning, the Role of Hydrogen–Deuterium Exchange Reactions and a New Pathway. Phys. Chem. Chem. Phys. 2015, 17, 6948– 6955, DOI: 10.1039/C4CP05626DGoogle Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXit1aquro%253D&md5=7d4dd3daa6fd88d8777f26838c395778HCN elimination from vinyl cyanide: product energy partitioning, the role of hydrogen-deuterium exchange reactions and a new pathwayVazquez, Saulo A.; Martinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (10), 6948-6955CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The different HCN elimination pathways from vinyl cyanide (VCN) are studied in this paper using RRKM, Kinetic Monte Carlo (KMC), and quasi-classical trajectory (QCT) calcns. A new HCN elimination pathway proves to be very competitive with the traditional 3-center and 4-center mechanisms, particularly at low excitation energies. However, low excitation energies have never been exptl. explored, and the high and low excitation regions are dynamically different. The KMC simulations carried out using singly deuterated VCN (CH2=CD-CN) at 148 kcal mol-1 show the importance of hydrogen-deuterium exchange reactions: both DCN and HCN will be produced in any of the 1,1 and 1,2 elimination pathways. The QCT simulation results obtained for the 3-center pathway are in agreement with the available exptl. results, with the 4-center results showing much more excitation of the products. In general, results seem to be consistent with a photodissocn. mechanism at 193 nm, where the mol. dissocs. (at least the HCN elimination pathways) in the ground electronic state. However, simulations assume that internal conversion is a fully statistical process, i.e., the HCN elimination channels proceed on the ground electronic state according to RRKM theory, which might not be the case. In future studies it would be of interest to include the photo-prepd. electronically excited state(s) in the dynamics simulations.
- 62Martínez-Núñez, E. An Automated Method to Find Transition States Using Chemical Dynamics Simulations. J. Comput. Chem. 2015, 36, 222– 234, DOI: 10.1002/jcc.23790Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGgtLbO&md5=e22946d4913acb912ffd139e36d6c11cAn automated method to find transition states using chemical dynamics simulationsMartinez-Nunez, EmilioJournal of Computational Chemistry (2015), 36 (4), 222-234CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A procedure to automatically find the transition states (TSs) of a mol. system (MS) is proposed. It has two components: high-energy chem. dynamics simulations (CDS), and an algorithm that analyzes the geometries along the trajectories to find reactive pathways. Two levels of electronic structure calcns. are involved: a low level (LL) is used to integrate the trajectories and also to optimize the TSs, and a higher level (HL) is used to reoptimize the structures. The method has been tested in three MSs: formaldehyde, formic acid (FA), and vinyl cyanide (VC), using MOPAC2012 and Gaussian09 to run the LL and HL calcns., resp. Both the efficacy and efficiency of the method are very good, with around 15 TS structures optimized every 10 trajectories, which gives a total of 7, 12, and 83 TSs for formaldehyde, FA, and VC, resp. The use of CDS makes it a powerful tool to unveil possible nonstatistical behavior of the system under study. © 2014 Wiley Periodicals, Inc.
- 63Martínez-Núñez, E. An Automated Transition State Search Using Classical Trajectories Initialized at Multiple Minima. Phys. Chem. Chem. Phys. 2015, 17, 14912– 14921, DOI: 10.1039/C5CP02175HGoogle Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnslOqsLo%253D&md5=695f6ea8566cc28afe6bb7c89a434bbeAn automated transition state search using classical trajectories initialized at multiple minimaMartinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (22), 14912-14921CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Very recently, we proposed an automated method for finding transition states of chem. reactions using dynamics simulations; the method has been termed Transition State Search using Chem. Dynamics Simulations (TSSCDS) (E. Martinez-Nunez, J. Comput. Chem., 2015, 36, 222-234). In the present work, an improved automated search procedure is developed, which consists of iteratively running different ensembles of trajectories initialized at different min. The iterative TSSCDS method is applied to the complex C3H4O system, obtaining a total of 66 different min. and 276 transition states. With the obtained transition states and paths, statistical RRKM calcns. and Kinetic Monte Carlo simulations are carried out to study the fragmentation dynamics of propenal, which is the global min. of the system. The kinetic simulations provide a (three-body dissocn.)/(CO elimination) ratio of 1.49 for an excitation energy of 148 kcal mol-1, which agrees well with the corresponding value obtained in the photolysis of propenal at 193 nm (1.1), suggesting that at least these two channels: three-body dissocn. (to give H2 + CO + C2H2) and CO elimination occur on the ground electronic state.
- 64Varela, J. A.; Vázquez, S. A.; Martínez-Núñez, E. An Automated Method to Find Reaction Mechanisms and Solve the Kinetics in Organometallic Catalysis. Chem. Sci. 2017, 8, 3843– 3851, DOI: 10.1039/C7SC00549KGoogle Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjsl2rtr8%253D&md5=df77d0eab3dac5fc42530661b1d57954An automated method to find reaction mechanisms and solve the kinetics in organometallic catalysisVarela, J. A.; Vazquez, S. A.; Martinez-Nunez, E.Chemical Science (2017), 8 (5), 3843-3851CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)A novel computational method is proposed in this work for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions. The method does not rely on either chem.intuition or assumed a priori mechanisms, and it works in a fully automated fashion. Its core is a procedure, recently developed by one of the authors, that combines accelerated direct dynamics with an efficient geometry-based post-processing algorithm to find transition states. In the present work, several auxiliary tools have been added to deal with the specific features of transition metal catalytic reactions. As a test case, we chose the cobalt-catalyzed hydroformylation of ethylene because of its well-established mechanism, and the fact that it has already been used in previous automated computational studies. Besides the generally accepted mechanism of Heck and Breslow, several side reactions, such as hydrogenation of the alkene, emerged from our calcns. Addnl., the calcd.rate law for the hydroformylation reaction agrees reasonably well with those obtained in previous exptl.and theor.studies.
- 65Rodriguez, A.; Rodriguez-Fernandez, R.; Vazquez, S. A.; Barnes, G. L.; Stewart, J. J. P.; Martinez-Nunez, E. tsscds2018: A Code for Automated Discovery of Chemical Reaction Mechanisms and Solving the Kinetics. J. Comput. Chem. 2018, 39, 1922– 1930, DOI: 10.1002/jcc.25370Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslOksr7J&md5=f0374c367acd28cb3cf2ebedb5ef3eeetsscds2018: A code for automated discovery of chemical reaction mechanisms and solving the kineticsRodriguez, Aurelio; Rodriguez-Fernandez, Roberto; A. Vazquez, Saulo; L. Barnes, George; J. P. Stewart, James; Martinez-Nunez, EmilioJournal of Computational Chemistry (2018), 39 (23), 1922-1930CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A new software, called tsscds2018, has been developed to discover reaction mechanisms and solve the kinetics in a fully automated fashion. The program employs algorithms based on Graph Theory to find transition state (TS) geometries from accelerated semiempirical dynamics simulations carried out with MOPAC2016. Then, the TSs are connected to the corresponding min. and the reaction network is obtained. Kinetic data like populations vs time or the abundancies of each product can also be obtained with our program thanks to a Kinetic Monte Carlo routine. Highly accurate ab initio potential energy diagrams and kinetics can also be obtained using an interface with Gaussian09. The source code is available on the following site: © 2018 Wiley Periodicals, Inc.
- 66Cerjan, C. J.; Miller, W. H. On Finding Transition States. J. Chem. Phys. 1981, 75, 2800– 2806, DOI: 10.1063/1.442352Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3MXltlyqsrY%253D&md5=62bc3d736a49a1df81c3f7b428117645On finding transition statesCerjan, Charles J.; Miller, William H.Journal of Chemical Physics (1981), 75 (6), 2800-6CODEN: JCPSA6; ISSN:0021-9606.An algorithm for locating transition states on a potential energy surface is described. The most important feature of the algorithm, which makes explicit use of the second deriv. matrix of the potential surface, is that it is able to "walk uphill" from the min. on a potential surface to the transition state essentially automatically. The method is illustrated by application to a two dimensional model problem, to the vinylidene-acetylene rearrangement (H2C = C:↔HC≡CH), and to the dissocn. and rearrangement of formaldehyde (H2CO↔H2 + O, HCOH). The algorithm is also seen to provide an improved way of following a reaction path from a transition state down to reactants or products.
- 67Simons, J.; Joergensen, P.; Taylor, H.; Ozment, J. Walking on Potential Energy Surfaces. J. Phys. Chem. 1983, 87, 2745– 2753, DOI: 10.1021/j100238a013Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3sXksF2it74%253D&md5=af251d7a8647c328879862fd7cde68a3Walking on potential energy surfacesSimons, Jack; Joergensen, Poul; Taylor, Hugh; Ozment, JudyJournal of Physical Chemistry (1983), 87 (15), 2745-53CODEN: JPCHAX; ISSN:0022-3654.By combining a local quadratic approxn. to the potential energy surface with the concept of a trust radius within which this quadratic approxn. is accurate and a scaling of one active coordinate, an automated surface walking algorithm was developed. This algorithm allows one to walk from geometries characteristic of equil. mol. structures, uphill along stream beds, through transition-state geometries, and onward to product-mol. equil. geometries. The method was appled to model and ab initio test cases with encouraging results. The success of using the algorithm in connection with approx. Hessian matrixes formed via so-called update techniques, which require only local force information, is esp. encouraging in light of the high cost of ab initio anal. evaluation of the Hessian.
- 68Davis, H. L.; Wales, D. J.; Berry, R. S. Exploring Potential Energy Surfaces with Transition State Calculations. J. Chem. Phys. 1990, 92, 4308– 4319, DOI: 10.1063/1.457790Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXit1elu74%253D&md5=c2ae2665bcc5e23802f289641cd94e3cExploring potential energy surfaces with transition state calculationsDavis, Heidi L.; Wales, David J.; Berry, R. StephenJournal of Chemical Physics (1990), 92 (7), 4308-19CODEN: JCPSA6; ISSN:0021-9606.Means are presented for using stationary points in two ways. One, for well-understood potentials, elucidates relations between the form of the surface and the dynamics that it supports, including the detn. of the effective mol. symmetry group. The other, for potentials of uncertain quality, provides a test for unphys. characteristics and suggests how the surface might be improved if it is found to be unsatisfactory in some respect. Our approach involves comparison of transition-state calcns. using the slowest-slide and Cerjan-Miller algorithms for two systems: the Lennard-Jones Ar7 cluster, and the Handy-Carter many-body-expansion potential for the ground state of formaldehyde.
- 69Wales, D. J. Basins of Attraction for Stationary Points on a Potential-Energy Surface. J. Chem. Soc., Faraday Trans. 1992, 88, 653– 657, DOI: 10.1039/ft9928800653Google ScholarThere is no corresponding record for this reference.
- 70Wales, D. J. Locating Stationary Points for Clusters in Cartesian Coordinates. J. Chem. Soc., Faraday Trans. 1993, 89, 1305– 1313, DOI: 10.1039/ft9938901305Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXksFKmu78%253D&md5=b823814bb89c8e62b4e904ae2d37b45dLocating stationary points for clusters in cartesian coordinatesWales, David J.Journal of the Chemical Society, Faraday Transactions (1993), 89 (9), 1305-13,4 platesCODEN: JCFTEV; ISSN:0956-5000.Location of min. and transition states on a potential energy surface by the eigenvector-following method using Cartesian coordinates and a projection operator is described. Comparisons with calcns. employing std. internal coordinates are made for a wide variety of model clusters. The new method, suggested by Baker and Hehre (1991), generally produces faster convergence and solves a no. of problems that are inherent when using distance, bond angle, and dihedral angle internal coordinates. In particular, eigenvector-following calcns. using analytic first and second energy derivs. should now be possible for much larger systems. Some example reaction paths are illustrated, including a new facetting rearrangement of 55- and 147-atom Mackay icosahedra. The basins of attraction of min. and transition states are also calcd., i.e., the regions of the potential-energy surface for which stationary-point searches converge to a given structure. The superiority of the projection operator approach is again demonstrated, and the previous observation that initial geometrical contraction is helpful in transition-state searches is confirmed.
- 71Jensen, F. Locating Transition Structures by Mode Following: A Comparison of Six Methods on the Ar8Lennard-Jones Potential. J. Chem. Phys. 1995, 102, 6706– 6718, DOI: 10.1063/1.469144Google ScholarThere is no corresponding record for this reference.
- 72Doye, J. P. K.; Wales, D. J. Surveying a Potential Energy Surface by Eigenvector-Following. Z. Phys. D: At., Mol. Clusters 1997, 40, 194– 197, DOI: 10.1007/s004600050192Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXjs12rtrw%253D&md5=affb326a8ca9636d1e24e1b5937b840eSurveying a potential energy surface by eigenvector-following. Applications to global optimization and the structural transformations of clustersDoye, J. P. K.; Wales, D. J.Zeitschrift fuer Physik D: Atoms, Molecules and Clusters (1997), 40 (1-4), 194-197CODEN: ZDACE2; ISSN:0178-7683. (Springer)We have developed a method to search potential energy surfaces which avoids some of the difficulties assocd. with trapping in local min. Steps are directly taken between min. using eigenvector-following. Exploration of this space by low temp. Metropolis Monte Carlo is a useful global optimization tool. This method successfully finds the lowest energy icosahedral min. of Lennard-Jones clusters from random starting configurations, but cannot find the global min. in a reasonable time for difficult cases such as the 38-atom Lennard-Jones cluster where the face-centered-cubic truncated octahedron is lowest in energy. However, by performing searches at higher temps., we have found a pathway between the truncated octahedron and the lowest energy icosahedral min. Such a pathway may be illustrative of some of the structural transformations that are obsd. for supported metal clusters by electron microscopy.
- 73Broyden, C. G. Quasi-Newton Methods and Their Application to Function Minimisation. Math. Comp. 1967, 21, 368– 381, DOI: 10.1090/S0025-5718-1967-0224273-2Google ScholarThere is no corresponding record for this reference.
- 74Munro, L. J.; Wales, D. J. Defect Migration in Crystalline Silicon. Phys. Rev. B: Condens. Matter Mater. Phys. 1999, 59, 3969– 3980, DOI: 10.1103/PhysRevB.59.3969Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXosVeltw%253D%253D&md5=a958a13eef54db0261a60a64d4e77e87Defect migration in crystalline siliconMunro, Lindsey J.; Wales, David J.Physical Review B: Condensed Matter and Materials Physics (1999), 59 (6), 3969-3980CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)A no. of vacancy and interstitial defect migration mechanisms were characterized for cryst. Si using supercells contg. 64 and 216 atoms and a tight-binding approach. The authors study various defect configurations corresponding to min. and the pathways that connect them. A modified eigenvector-following approach was used to locate true transition states. The authors exploit the fact that only one Hessian eigenvector is needed to define the uphill search direction and use conjugate gradient minimization in the tangent space to produce a hybrid algorithm. Two implementations of this approach are considered, the 1st where 2nd derivs. are available but full diagonalization of the Hessian would be the most time-consuming step, and the 2nd where only 1st derivs. of the energy are known.
- 75Malek, R.; Mousseau, N. Dynamics of Lennard-Jones Clusters: A Characterization of the Activation-Relaxation Technique. Phys. Rev. E: Stat. Phys., Plasmas, Fluids, Relat. Interdiscip. Top. 2000, 62, 7723– 7728, DOI: 10.1103/PhysRevE.62.7723Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXoslahurw%253D&md5=73391e2c5502b4312a8cdd0f07852b91Dynamics of Lennard-Jones clusters: A characterization of the activation-relaxation techniqueMalek, Rachid; Mousseau, NormandPhysical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics (2000), 62 (6-A), 7723-7728CODEN: PLEEE8; ISSN:1063-651X. (American Physical Society)The potential energy surface of Lennard-Jones clusters is investigated using the activation-relaxation technique (ART). This method defines events in the configurational energy landscape as a two-step process: (a) a configuration is first activated from a local min. to a nearby saddle-point, and (b) is then relaxed to a new min. Although ART has been applied with success to a wide range of materials such as a-Si, a-SiO2, and binary Lennard-Jones glasses, questions remain regarding the biases of the technique. We address some of these questions in a detailed study of ART-generated events in Lennard-Jones clusters, a system for which much is already known. In particular, we study the distribution of saddle-points, the pathways between configurations, and the reversibility of paths. We find that ART can identify all trajectories with a first-order saddle point leaving a given min., is fully reversible, and samples events following the Boltzmann wt. at the saddle point.
- 76Deglmann, P.; Furche, F. Efficient Characterization of Stationary Points on Potential Energy Surfaces. J. Chem. Phys. 2002, 117, 9535– 9538, DOI: 10.1063/1.1523393Google Scholar76https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XovVSru78%253D&md5=3bbd5b3b826d7210588dbb7121b72176Efficient characterization of stationary points on potential energy surfacesDeglmann, Peter; Furche, FilippJournal of Chemical Physics (2002), 117 (21), 9535-9538CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Traditional methods for characterizing an optimized mol. structure as a min. or as a saddle point on the nuclear potential energy surface require the full Hessian. However, if f denotes the no. of nuclear degrees of freedom, a full Hessian calcn. is more expensive than a single point geometry optimization step by the order of magnitude of f. Here we present a method which allows to det. the lowest vibrational frequencies of a mol. at significantly lower cost. Our approach takes advantage of the fact that only a few perturbed first-order wave functions need to be computed in an iterative diagonalization scheme instead of f ones in a full Hessian calcn. We outline an implementation for Hartree-Fock and d. functional methods. Applications indicate a scaling similar to that of a single point energy or gradient calcn., but with a larger prefactor. Depending on the no. of soft vibrational modes, the iterative method becomes effective for systems with more than 30-50 atoms.
- 77Reiher, M.; Neugebauer, J. A Mode-Selective Quantum Chemical Method for Tracking Molecular Vibrations Applied to Functionalized Carbon Nanotubes. J. Chem. Phys. 2003, 118, 1634– 1641, DOI: 10.1063/1.1523908Google Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjtVaquw%253D%253D&md5=616ea82fd0a616e1c7c6428c4581da7bA mode-selective quantum chemical method for tracking molecular vibrations applied to functionalized carbon nanotubesReiher, Markus; Neugebauer, JohannesJournal of Chemical Physics (2003), 118 (4), 1634-1641CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The theor. investigation of mesoscopic objects requires new techniques which are particularly suited for the study of selected aspects of these systems. Vibrational spectroscopy is a main source for structural information on heterogeneous systems. We present an efficient quantum chem. method, which relies on a modified Davidson algorithm for targeting selected vibrations in IR and Raman spectra. This approach is applied to the characteristic breathing modes of single-walled carbon nanotubes.
- 78Sharada, S. M.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Automated Transition State Searches without Evaluating the Hessian. J. Chem. Theory Comput. 2012, 8, 5166– 5174, DOI: 10.1021/ct300659dGoogle ScholarThere is no corresponding record for this reference.
- 79Bergeler, M.; Herrmann, C.; Reiher, M. Mode-Tracking Based Stationary-Point Optimization. J. Comput. Chem. 2015, 36, 1429– 1438, DOI: 10.1002/jcc.23958Google Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpvFWgt7c%253D&md5=50ae502b58d1b2eb8f04225407e085afMode-tracking based stationary-point optimizationBergeler, Maike; Herrmann, Carmen; Reiher, MarkusJournal of Computational Chemistry (2015), 36 (19), 1429-1438CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)In this work, we present a transition-state optimization protocol based on the Mode-Tracking algorithm [Reiher and Neugebauer, J. Chem. Phys., 2003, 118, 1634]. By calcg. only the eigenvector of interest instead of diagonalizing the full Hessian matrix and performing an eigenvector following search based on the selectively calcd. vector, we can efficiently optimize transition-state structures. The initial guess structures and eigenvectors are either chosen from a linear interpolation between the reactant and product structures, from a nudged-elastic band search, from a constrained-optimization scan, or from the min.-energy structures. Alternatively, initial guess vectors based on chem. intuition may be defined. We then iteratively refine the selected vectors by the Davidson subspace iteration technique. This procedure accelerates finding transition states for large mols. of a few hundred atoms. It is also beneficial in cases where the starting structure is very different from the transition-state structure or where the desired vector to follow is not the one with lowest eigenvalue. Explorative studies of reaction pathways are feasible by following manually constructed mol. distortions. © 2015 Wiley Periodicals, Inc.
- 80Halgren, T. A.; Lipscomb, W. N. The Synchronous-Transit Method for Determining Reaction Pathways and Locating Molecular Transition States. Chem. Phys. Lett. 1977, 49, 225– 232, DOI: 10.1016/0009-2614(77)80574-5Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXlsFWmtLs%253D&md5=90c0d95b096220fddcc7eebc0639fdfdThe synchronous-transit method for determining reaction pathways and locating molecular transition statesHalgren, Thomas A.; Lipscomb, William N.Chemical Physics Letters (1977), 49 (2), 225-32CODEN: CHPLBC; ISSN:0009-2614.In the synchronous-transit method, a model linear synchronous transit pathway is first constructed and is then refined by optimizing 1 or more intermediate structures subject to the constraint that the optimized structure retain the same relative position along the path orthogonal optimization. The method yields a series of energy ests. which progressively bound the energy of the transition state from above and from below. High computational efficiency is attainable, and sufficient flexibility is provided to deal with asynchronous processes. Comparisons are made to the alternative reaction-coordinate approach. The method is applied to a model 2-dimensional energy surface and to the allowed electrocyclic interconversions of the cyclopropyl and allyl cations and of cyclobutene and cis-butadiene.
- 81Ayala, P. Y.; Schlegel, H. B. A Combined Method for Determining Reaction Paths, Minima, and Transition State Geometries. J. Chem. Phys. 1997, 107, 375– 384, DOI: 10.1063/1.474398Google Scholar81https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXksVeksrY%253D&md5=2ec17a4bf9a0f0f848e6fe0b844fe250A combined method for determining reaction paths, minima, and transition state geometriesAyala, Philippe Y.; Schlegel, H. BernhardJournal of Chemical Physics (1997), 107 (2), 375-384CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Mapping out a reaction mechanism involves optimizing the reactants and products, finding the transition state and following the reaction path connecting them. Transition states can be difficult to locate and reaction paths can be expensive to follow. We describe an efficient algorithm for detg. the transition state, min. and reaction path in a single procedure. Starting with an approx. path represented by N points, the path is iteratively relaxed until one of the N points reached the transition state, the end points optimize to min. and the remaining points converged to a second order approxn. of the steepest descent path. The method appears to be more reliable than conventional transition state optimization algorithms, and requires only energies and gradients, but not second deriv. calcns. The procedure is illustrated by application to a no. of model reactions. In most cases, the reaction mechanism can be described well using 5 to 7 points to represent the transition state, the min. and the path. The computational cost of relaxing the path is less than or comparable to the cost of std. techniques for finding the transition state and the min., detg. the transition vector and following the reaction path on both sides of the transition state.
- 82Henkelman, G.; Jónsson, H. A Dimer Method for Finding Saddle Points on High Dimensional Potential Surfaces Using Only First Derivatives. J. Chem. Phys. 1999, 111, 7010– 7022, DOI: 10.1063/1.480097Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXmt1Ojurc%253D&md5=d3628bc9e56615b91730dd2224a36723A dimer method for finding saddle points on high dimensional potential surfaces using only first derivativesHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (1999), 111 (15), 7010-7022CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The problem of detg. which activated (and slow) transitions can occur from a given initial state at a finite temp. is addressed. In the harmonic approxn. to transition state theory this problem reduces to finding the set of low lying saddle points at the boundary of the potential energy basin assocd. with the initial state, as well as the relevant vibrational frequencies. Also, when full transition state theory calcns. are carried out, it can be useful to know the location of the saddle points on the potential energy surface. A method for finding saddle points without knowledge of the final state of the transition is described. The method only makes use of first derivs. of the potential energy and is, therefore, applicable in situations where second derivs. are too costly or too tedious to evaluate, for example, in plane wave based d. functional theory calcns. It is also designed to scale efficiently with the dimensionality of the system and can be applied to very large systems when empirical or semiempirical methods are used to obtain the at. forces. The method can be started from the potential min. representing the initial state, or from an initial guess closer to the saddle point. An application to Al adatom diffusion on an Al(100) surface described by an embedded atom method potential is presented. A large no. of saddle points were found for adatom diffusion and dimer/vacancy formation. A surprisingly low energy four atom exchange process was found as well as processes indicative of local hex reconstruction of the surface layer.
- 83Henkelman, G.; Uberuaga, B. P.; Jónsson, H. A Climbing Image Nudged Elastic Band Method for Finding Saddle Points and Minimum Energy Paths. J. Chem. Phys. 2000, 113, 9901– 9904, DOI: 10.1063/1.1329672Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagurc%253D&md5=3899b9e2e9e3eb74009987d96623f018A climbing image nudged elastic band method for finding saddle points and minimum energy pathsHenkelman, Graeme; Uberuaga, Blas P.; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9901-9904CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)A modification of the nudged elastic band method for finding min. energy paths is presented. One of the images is made to climb up along the elastic band to converge rigorously on the highest saddle point. Also, variable spring consts. are used to increase the d. of images near the top of the energy barrier to get an improved est. of the reaction coordinate near the saddle point. Applications to CH4 dissociative adsorption on Ir(111) and H2 on Si(100) using plane wave based d. functional theory are presented.
- 84Henkelman, G.; Jónsson, H. Improved Tangent Estimate in the Nudged Elastic Band Method for Finding Minimum Energy Paths and Saddle Points. J. Chem. Phys. 2000, 113, 9978– 9985, DOI: 10.1063/1.1323224Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagu7Y%253D&md5=57dbeadabf6061460912090f40b581e0Improved tangent estimate in the nudged elastic band method for finding minimum energy paths and saddle pointsHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9978-9985CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)An improved way of estg. the local tangent in the nudged elastic band method for finding min. energy paths is presented. In systems where the force along the min. energy path is large compared to the restoring force perpendicular to the path and when many images of the system are included in the elastic band, kinks can develop and prevent the band from converging to the min. energy path. We show how the kinks arise and present an improved way of estg. the local tangent which solves the problem. The task of finding an accurate energy and configuration for the saddle point is also discussed and examples given where a complementary method, the dimer method, is used to efficiently converge to the saddle point. Both methods only require the first deriv. of the energy and can, therefore, easily be applied in plane wave based d.-functional theory calcns. Examples are given from studies of the exchange diffusion mechanism in a Si crystal, Al addimer formation on the Al(100) surface, and dissociative adsorption of CH4 on an Ir(111) surface.
- 85Maragakis, P.; Andreev, S. A.; Brumer, Y.; Reichman, D. R.; Kaxiras, E. Adaptive Nudged Elastic Band Approach for Transition State Calculation. J. Chem. Phys. 2002, 117, 4651– 4658, DOI: 10.1063/1.1495401Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmsVWntbo%253D&md5=9645dcee50aacfef2aa9265a1989ac1eAdaptive nudged elastic band approach for transition state calculationMaragakis, P.; Andreev, Stefan A.; Brumer, Yisroel; Reichman, David R.; Kaxiras, EfthimiosJournal of Chemical Physics (2002), 117 (10), 4651-4658CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)We present a method for the location of transition states in complicated phys. systems. Our algorithm is a variation of the well-established nudged elastic band method and leads to significant improvements in efficiency and accuracy. We assess the applicability of our method by testing it on several systems of practical interest representing a variety of phys. situations. At the mol. level, we apply the method to tautomerization processes in nucleic acid bases and the double proton transfer in nucleic acid base pairs. For bulk systems, we considered the concerted exchange mechanism in Si, which is a complicated pathway for defect-free diffusion in the diamond lattice. For surface systems, we considered ad-dimer diffusion mechanisms on Si(100). We incorporated the climbing image extension of the nudged elastic band method and compared it against the original approach on two-dimensional model potential energy surfaces. Based on favorable comparisons with related methods and the general implementation of our method, we believe that this is well suited for efficient ests. of activation barriers with sophisticated electronic structure codes.
- 86E, W.; Ren, W.; Vanden-Eijnden, E. String Method for the Study of Rare Events. Phys. Rev. B: Condens. Matter Mater. Phys. 2002, 66, 052301, DOI: 10.1103/PhysRevB.66.052301Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmvVSlurg%253D&md5=1c24a86bf403c333e9705f00876e4aa3String method for the study of rare eventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricPhysical Review B: Condensed Matter and Materials Physics (2002), 66 (5), 052301/1-052301/4CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)We present an efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e., smooth curves with intrinsic parametrization whose dynamics takes them to the most probable transition path between two metastable regions in configuration space. Free energy barriers and transition rates can then be detd. by a std. umbrella sampling around the string. Applications to Lennard-Jones cluster rearrangement and thermally induced switching of a magnetic film are presented.
- 87E, W.; Ren, W.; Vanden-Eijnden, E. Finite Temperature String Method for the Study of Rare Events. J. Phys. Chem. B 2005, 109, 6688– 6693, DOI: 10.1021/jp0455430Google Scholar87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFSnsbo%253D&md5=f92a743d5d4b946756c04c6c1cbc8a8dFinite Temperature String Method for the Study of Rare EventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricJournal of Physical Chemistry B (2005), 109 (14), 6688-6693CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)A method is presented for the study of rare events such as conformational changes arising in activated processes whose reaction coordinate is not known beforehand and for which the assumptions of transition state theory are invalid. The method samples the energy landscape adaptively and dets. the isoprobability surfaces for the transition: by definition the trajectories initiated anywhere on one of these surfaces has equal probability to reach first one metastable set rather than the other. Upon weighting these surfaces by the equil. probability distribution, one obtains an effective transition pathway, i.e., a tube in configuration space inside which conformational changes occur with high probability, and the assocd. rate. The method is first validated on a simple two-dimensional example; then it is applied to a model of solid-solid transformation of a condensed system.
- 88Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Efficient Exploration of Reaction Paths via a Freezing String Method. J. Chem. Phys. 2011, 135, 224108, DOI: 10.1063/1.3664901Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1SkurrN&md5=01c0f45d3455f92d1341022377717530Efficient exploration of reaction paths via a freezing string methodBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Physics (2011), 135 (22), 224108/1-224108/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The ability to efficiently locate transition states is critically important to the widespread adoption of theor. chem. techniques for their ability to accurately predict kinetic consts. Existing surface walking techniques to locate such transition states typically require an extremely good initial guess that is often beyond intuition to est. To alleviate this problem, automated techniques to locate transition state guesses have been created that take the known reactant and product endpoint structures as inputs. In this work, we present a simple method to build an approx. reaction path through a combination of interpolation and optimization. Starting from the known reactant and product structures, new nodes are interpolated inwards towards the transition state, partially optimized orthogonally to the reaction path, and then frozen before a new pair of nodes is added. The algorithm is stopped once the string ends connect. For the practical user, this method provides a quick and convenient way to generate transition state structure guesses. Tests on three reactions (cyclization of cis,cis-2,4-hexadiene, alanine dipeptide conformation transition, and ethylene dimerization in a Ni-exchanged zeolite) show that this "freezing string" method is an efficient way to identify complex transition states with significant cost savings over existing methods, particularly when high quality linear synchronous transit interpolation is employed. (c) 2011 American Institute of Physics.
- 89Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Incorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and Applications. J. Chem. Theory Comput. 2011, 7, 4019– 4025, DOI: 10.1021/ct200654uGoogle Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOqurjE&md5=f76c6427d713c0375114e0262ef0d29eIncorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and ApplicationsBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Theory and Computation (2011), 7 (12), 4019-4025CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method is a powerful tool in the systematic study of chem. reactions with theor. methods which allows for the rapid identification of transition states connecting known reactant and product structures. However, the efficiency of this method is heavily influenced by the choice of interpolation scheme when adding new nodes to the string during optimization. In particular, the use of Cartesian coordinates with cubic spline interpolation often produces guess structures which are far from the final reaction path and require many optimization steps (and thus many energy and gradient calcns.) to yield a reasonable final structure. In this paper, we present a new method for interpolating and reparameterizing nodes within the growing string method using the linear synchronous transit method of Halgren and Lipscomb. When applied to the alanine dipeptide rearrangement and a simplified cationic alkyl ring condensation reaction, a significant speedup in terms of computational cost is achieved (30-50%).
- 90Zimmerman, P. Reliable Transition State Searches Integrated with the Growing String Method. J. Chem. Theory Comput. 2013, 9, 3043– 3050, DOI: 10.1021/ct400319wGoogle Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptFeht78%253D&md5=6f5715237172541a74de71a1781cee83Reliable Transition State Searches Integrated with the Growing String MethodZimmerman, PaulJournal of Chemical Theory and Computation (2013), 9 (7), 3043-3050CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method (GSM) is highly useful for locating reaction paths connecting two mol. intermediates. GSM has often been used in a two-step procedure to locate exact transition states (TS), where GSM creates a quality initial structure for a local TS search. This procedure and others like it, however, do not always converge to the desired transition state because the local search is sensitive to the quality of the initial guess. This article describes an integrated technique for simultaneous reaction path and exact transition state search. This is achieved by implementing an eigenvector following optimization algorithm in internal coordinates with Hessian update techniques. After partial convergence of the string, an exact saddle point search begins under the constraint that the maximized eigenmode of the TS node Hessian has significant overlap with the string tangent near the TS. Subsequent optimization maintains connectivity of the string to the TS as well as locks in the TS direction, all but eliminating the possibility that the local search leads to the wrong TS. To verify the robustness of this approach, reaction paths and TSs are found for a benchmark set of more than 100 elementary reactions.
- 91Vaucher, A. C.; Reiher, M. Minimum Energy Paths and Transition States by Curve Optimization. J. Chem. Theory Comput. 2018, 14, 3091– 3099, DOI: 10.1021/acs.jctc.8b00169Google Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnsF2qtbg%253D&md5=88c0d81d005d0b913d9b75341576889dMinimum Energy Paths and Transition States by Curve OptimizationVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (6), 3091-3099CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Transition states and min. energy paths are essential to understand and predict chem. reactivity. Double-ended methods represent a std. approach for their detn. A new double-ended method that optimizes reaction paths described by curves is introduced. Unlike other methods, the approach optimizes the curve parameters rather than distinct structures along the path. With mol. paths represented as continuous curves, the optimization can benefit from the advantages of an integral-based formulation. This approach is called ReaDuct and its applicability for mol. paths parametrized by B-spline curves is demonstrated.
- 92Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and Rates. Ind. Eng. Chem. Res. 1994, 33, 790– 799, DOI: 10.1021/ie00028a003Google Scholar92https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXitFKnu7s%253D&md5=7cfd4d0b5f978bbea1c40e00eadcbf77Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and RatesBroadbelt, Linda J.; Stark, Scott M.; Klein, Michael T.Industrial & Engineering Chemistry Research (1994), 33 (4), 790-9CODEN: IECRED; ISSN:0888-5885.The development of an integrated system for the computer generation of kinetic models is described. Required input is the structure of the reactants, the reaction rules, and the parameters of a structure/property kinetics correlation. The algorithm transforms this information into reactant/product relationships, i.e., the reaction network, species properties, rate consts., and the FORTRAN code corresponding to the governing species' balance equations, and offers a soln. capability. Graph theory is exploited to represent the constituent atoms of a mol. to allow detn. of species' uniqueness, implement chem. reactions, and identify reaction products. Special attention was devoted to improved algorithm efficiencies, the handling of ring systems, and "on-the-fly" quantum chem. calcns. This general approach is described in using ethane and cyclohexane pyrolysis case studies. The increase in the no. of equations and no. of components for ethane pyrolysis was exponential with the carbon no. of allowed species.
- 93Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Reaction Modelling: Decomposition and Encoding Algorithms for Determining Species Uniqueness. Comput. Chem. Eng. 1996, 20, 113– 129, DOI: 10.1016/0098-1354(94)00009-DGoogle Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1yjsL0%253D&md5=12e4ffb130284518319665befc664e09Computer generated reaction modeling: decomposition and encoding algorithms for determining species uniquenessBroadbelt, L. J.; Stark, S. M.; Klein, M. T.Computers & Chemical Engineering (1996), 20 (2), 113-29CODEN: CCENDW; ISSN:0098-1354. (Elsevier)The concept of computer generated reaction modeling was broadened through the development of a general planar graph algorithm for detn. of isomorphism. The previous capability was limited by its inability to det. the uniqueness of ring-contg. species unambiguously, restricting the application of automatic network generation to non-cyclic species or cyclic species where the ring was not involved in the chem. transformation. In this work, the systematic identification of both noncyclic and cyclic species was carried out by constructing the structurally explicit decompn. tree, an assembly of the biconnected components of the graph, from which a graph invariant unique string code was obtained by iteratively encoding and ordering the subtrees of the decompn. tree. A lexicog. comparison of the unique string code of the candidate species with the string codes of all previously generated species with the same empirical formula allowed unambiguous detn. of species uniqueness.
- 94Broadbelt, L. J.; Pfaendtner, J. Lexicography of Kinetic Modeling of Complex Reaction Networks. AIChE J. 2005, 51, 2112– 2121, DOI: 10.1002/aic.10599Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslCnt7c%253D&md5=47e8076ea9b3fde03f4c063e018a1131Lexicography of kinetic modeling of complex reaction networksBroadbelt, Linda J.; Pfaendtner, JimAIChE Journal (2005), 51 (8), 2112-2121CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)Lexicog. of kinetic modeling of complex reaction networks is discussed.
- 95Evans, M. G.; Polanyi, M. Inertia and Driving Force of Chemical Reactions. Trans. Faraday Soc. 1938, 34, 11– 24, DOI: 10.1039/tf9383400011Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaA1cXitVWisg%253D%253D&md5=1b35420fa6bfc7cd2c1118fb7a7096ebInertia and driving force of chemical reactionsEvans, M. G.; Polanyi, M.Transactions of the Faraday Society (1938), 34 (), 11-24CODEN: TFSOA4; ISSN:0014-7672.A reaction has "inertia" if the activation energy is exothermic and has a "driving force" when the formation of new bonds lowers the activation energy. The energy surfaces of the initial and final states and the reaction paths between them as well as their relation to at. repulsions are considered.
- 96Matheu, D. M.; Dean, A. M.; Grenda, J. M.; Green, W. H. Mechanism Generation with Integrated Pressure Dependence: A New Model for Methane Pyrolysis. J. Phys. Chem. A 2003, 107, 8552– 8565, DOI: 10.1021/jp0345957Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXnsVehtLk%253D&md5=087a6a72c1556f599dbf81547530cddeMechanism Generation with Integrated Pressure Dependence: A New Model for Methane PyrolysisMatheu, David M.; Dean, Anthony M.; Grenda, Jeffrey M.; Green, William H., Jr.Journal of Physical Chemistry A (2003), 107 (41), 8552-8565CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Autocatalytic, lower-temp. (≤1100 K) methane pyrolysis has defied mechanistic explanation for almost three decades. The most recent attempt (by Dean in 1990) invoked the chem. activated addn. of an allyl radical to acetylene, leading to a cyclopentadiene/cyclopentadienyl chain-branching system that prompted the obsd. autocatalysis. However, newer, more accurate thermochem. data for the cyclopentadienyl radical render that explanation untenable. A new model for methane pyrolysis is constructed here, using a novel mechanism generation approach that automatically computes any needed rate consts. k(T,P) for chem. or thermally activated pressure-dependent reactions. The computer-generated mechanism accurately predicts the obsd. autocatalysis and concn. profiles without any adjustable parameters. Radical-forming reverse disproportionation reactions-which involve propyne, allene, and fulvene-account for at least half of the exptl. obsd. autocatalytic effect. Many of these reverse disproportionations were neglected in previous studies. The cyclopentadienyl radical is also important, but it is formed primarily by the chem. activated reaction of propargyl with acetylene. New rate ests. for unimol. ring-closure reactions of unsatd. radicals are also presented. This approach is the first to incorporate pressure-dependent reactions generally and systematically during computerized mechanism construction. It successfully identifies complex but crit. chem.-reaction pathways and autocatalytic loops missed by experienced kineticists.
- 97Gao, C. W.; Allen, J. W.; Green, W. H.; West, R. H. Reaction Mechanism Generator: Automatic Construction of Chemical Kinetic Mechanisms. Comput. Phys. Commun. 2016, 203, 212– 225, DOI: 10.1016/j.cpc.2016.02.013Google Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs12kur4%253D&md5=3403c82513d617761ce38eb7de35c5c3Reaction Mechanism Generator: Automatic construction of chemical kinetic mechanismsGao, Connie W.; Allen, Joshua W.; Green, William H.; West, Richard H.Computer Physics Communications (2016), 203 (), 212-225CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier B.V.)Reaction Mechanism Generator (RMG) constructs kinetic models composed of elementary chem. reaction steps using a general understanding of how mols. react. Species thermochem. is estd. through Benson group additivity and reaction rate coeffs. are estd. using a database of known rate rules and reaction templates. At its core, RMG relies on two fundamental data structures: graphs and trees. Graphs are used to represent chem. structures, and trees are used to represent thermodn. and kinetic data. Models are generated using a rate-based algorithm which excludes species from the model based on reaction fluxes. RMG can generate reaction mechanisms for species involving carbon, hydrogen, oxygen, sulfur, and nitrogen. It also has capabilities for estg. transport and solvation properties, and it automatically computes pressure-dependent rate coeffs. and identifies chem.-activated reaction paths. RMG is an object-oriented program written in Python, which provides a stable, robust programming architecture for developing an extensible and modular code base with a large suite of unit tests. Computationally intensive functions are cythonized for speed improvements.
- 98Harper, M. R.; Van Geem, K. M.; Pyl, S. P.; Marin, G. B.; Green, W. H. Comprehensive Reaction Mechanism for N-Butanol Pyrolysis and Combustion. Combust. Flame 2011, 158, 16– 41, DOI: 10.1016/j.combustflame.2010.06.002Google Scholar98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVWht7zI&md5=73235ccdbc0fdce97f3c1a8b423bc3bbComprehensive reaction mechanism for n-butanol pyrolysis and combustionHarper, Michael R.; Van Geem, Kevin M.; Pyl, Steven P.; Marin, Guy B.; Green, William H.Combustion and Flame (2011), 158 (1), 16-41CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)A detailed reaction mechanism for n-butanol, consisting of 263 species and 3381 reactions, has been generated using the open-source software package, Reaction Mechanism Generator (RMG). The mechanism is tested against recently published data - jet-stirred reactor mole fraction profiles, opposed-flow diffusion flame mole fraction profiles, autoignition delay times, and doped methane diffusion flame mole fraction profiles - and newly acquired n-butanol pyrolysis expts. with very encouraging results. The chem. of butanal is also validated against autoignition delay times obtained in shock tube expts. A flux and sensitivity anal. for each simulated dataset is discussed and reveals important reactions where more accurate rate const. ests. were required. New rate const. expressions were computed using quantum chem. and transition state theory calcns. Furthermore, in addn. to comparing the proposed model with the eight datasets, the model is also compared with recently published n-butanol models for three of the datasets. Key differences between the proposed model and the published models are discussed.
- 99van Geem, K. M.; Reyniers, M.-F.; Marin, G. B.; Song, J.; Green, W. H.; Matheu, D. M. Automatic Reaction Network Generation Using RMG for Steam Cracking of N-hexane. AIChE J. 2006, 52, 718– 730, DOI: 10.1002/aic.10655Google Scholar99https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xht1Ogu7s%253D&md5=d20f9949dd0516d2ef7b2bba4d919fa5Automatic reaction network generation using RMG for steam cracking of n-hexaneVan Geem, Kevin M.; Reyniers, Marie-Francoise; Marin, Guy B.; Song, Jing; Green, William H.; Matheu, David M.AIChE Journal (2006), 52 (2), 718-730CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)A new reaction mechanism generator RMG is used to automatically construct a pressure dependent kinetic model for the steam cracking of n-hexane. Comparison between simulated and pilot plant data shows that RMG is able to generate detailed reaction networks that accurately predict the conversion and the yields of the major products although none of the kinetic parameters are fit to the expts. RMG generates reaction networks based on minimal assumptions, making it possible to test commonly used assumptions such as the μ-hypothesis and the quasi steady-state approxn. (QSSA) for μ-radicals, traditionally used in steam cracking,1,2 as well as in pyrolysis. The RMG-reaction network for n-hexane confirms that no bimol. reactions of heavy radical species are important at the examd. conditions (COT: 953 K - 1090 K; COP: 0.20 MPa -0.24 MPa; <80% conversion), and that the QSSA for the group of μ-radicals leads to negligible errors. RMG also offers the possibility to est. the error introduced by neglecting the pressure dependence of most of the reactions. In the case studied, this frequently made (but seldom tested) approxn. appears to be justified.
- 100Petway, S. V.; Ismail, H.; Green, W. H.; Estupiñán, E. G.; Jusinski, L. E.; Taatjes, C. A. Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl Radical. J. Phys. Chem. A 2007, 111, 3891– 3900, DOI: 10.1021/jp0668549Google Scholar100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXkt1Ortrk%253D&md5=65ea9d850eea1b016f8f57d241479b04Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl RadicalPetway, Sarah V.; Ismail, Huzeifa; Green, William H.; Estupinan, Edgar G.; Jusinski, Leonard E.; Taatjes, Craig A.Journal of Physical Chemistry A (2007), 111 (19), 3891-3900CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Prodn. of OH in the reaction of the neopentyl radical with O2 has been measured by a laser photolysis/cw absorption method for various pressures and oxygen concns. at 673, 700, and 725 K. The MIT Reaction Mechanism Generator (RMG) was used to automatically generate a model for this system, and the predicted OH concn. profiles are compared to present and literature exptl. results. Several reactions significantly affect the OH profile. The exptl. data provide useful constraints on the rate coeff. for the formally direct chem. activation reaction of neopentyl radical with O2 to form OH (CH3)3CCH2 + O2 → OH + 3,3-dimethyloxetane (Rxn 1) At 673 K and 60 Torr, log k1 (cm3 mol.-1 s-1) = -13.7 ± 0.5. Abs. absorbance measurements on OH and I indicate that the branching ratio for R + O2 to OH is about 0.03 under these conditions. The data suggest that the ab initio neopentyl + O2 potential energy surface of Sun and Bozzelli is accurate to within 2 kcal mol-1.
- 101Hansen, N.; Merchant, S. S.; Harper, M. R.; Green, W. H. The Predictive Capability of an Automatically Generated Combustion Chemistry Mechanism: Chemical Structures of Premixed Iso-Butanol Flames. Combust. Flame 2013, 160, 2343– 2351, DOI: 10.1016/j.combustflame.2013.05.013Google Scholar101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXpsV2ksbY%253D&md5=e7e16e09c9c3b50328ce0686d91b3b37The predictive capability of an automatically generated combustion chemistry mechanism: Chemical structures of premixed iso-butanol flamesHansen, Nils; Merchant, Shamel S.; Harper, Michael R.; Green, William H.Combustion and Flame (2013), 160 (11), 2343-2351CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)The chem. compns. of four low-pressure premixed flames of iso-butanol are investigated with an emphasis on assessing the predictive capabilities of an automatically generated combustion chem. model. This kinetic model had been extensively tested against earlier exptl. data [S.S. Merchant, E.F. Zanoelo, R.L. Speth, M.R. Harper, K.M. Van Geem, W.H. Green, Combust. Flame (2013), http://dx.doi.org/10.1016/j.combustflame.2013.04.023.] and also shows impressive capabilities for predicting the new flame data presented here. The new set of data consists of isomer-resolved mole fraction profiles for more than 40 species in each of the four flames and provides a comprehensive benchmark for testing of any combustion chem. model for iso-butanol. Isomer-specificity is achieved by analyzing flames, which are burner-stabilized at equivalence ratios of .vphi. = 1.0-1.5 and at pressures between 15-30 Torr, with mol.-beam mass spectrometry and single-photon ionization by tunable vacuum-UV synchrotron radiation. Predictions of the C2H4O, C3H6O, and C4H8O enol-aldehyde-ketone isomers are improved compared to the earlier work by Hansen et al. [N. Hansen, M. R. Harper, W. H. Green, Phys. Chem. Chem. Phys. 13 (2011) 20262-20274] on similar n-butanol flames. A reaction path anal. identifies prominent fuel-consumption and oxidn. sequences. Almost all of the species mole fraction data reported here are predicted within the measurement uncertainties of a factor of two to three. Some significant differences with previous published models are highlighted.
- 102Slakman, B. L.; Simka, H.; Reddy, H.; West, R. H. Extending Reaction Mechanism Generator to Silicon Hydride Chemistry. Ind. Eng. Chem. Res. 2016, 55, 12507– 12515, DOI: 10.1021/acs.iecr.6b02402Google Scholar102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslOhsr%252FI&md5=51d944ea4978704bfbe0e0f68e7e0ca0Extending Reaction Mechanism Generator to Silicon Hydride ChemistrySlakman, Belinda L.; Simka, Harsono; Reddy, Harinath; West, Richard H.Industrial & Engineering Chemistry Research (2016), 55 (49), 12507-12515CODEN: IECRED; ISSN:0888-5885. (American Chemical Society)Understanding the gas-phase chem. of Si hydrides is the 1st step to building a realistic kinetic model for chem. vapor deposition (CVD). Functionality for thermodn. and kinetic data estn. of Si hydrides was added to the open-source software Reaction Mechanism Generator (RMG). Using the updated RMG, a detailed kinetic model was built for SiH4 thermal decompn. The generated model was used to perform reactor simulations at various process conditions for comparison to prior SiH4 decompn. expts. in a flow tube. Results show that the RMG-generated model can reasonably replicate exptl. results for SiH4 concn. profiles at different temps. and residence times. While the effect of changing initial SiH4 concn. is not captured, a 1st pass sensitivity anal. reveals that reasonable errors in reaction rates could contribute to the discrepancy.
- 103Seyedzadeh Khanshan, F.; West, R. H. Developing Detailed Kinetic Models of Syngas Production from Bio-Oil Gasification Using Reaction Mechanism Generator (RMG). Fuel 2016, 163, 25– 33, DOI: 10.1016/j.fuel.2015.09.031Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFersbjJ&md5=40a7d6183fcf086f287431148682cde2Developing detailed kinetic models of syngas production from bio-oil gasification using Reaction Mechanism Generator (RMG)Seyedzadeh Khanshan, Fariba; West, Richard H.Fuel (2016), 163 (), 25-33CODEN: FUELAC; ISSN:0016-2361. (Elsevier Ltd.)Detailed kinetic models for the conversion of bio-oil to syngas through gasification were developed automatically using the open source software package Reaction Mechanism Generator (RMG). The influences of process operating conditions and of RMG parameters on the performance of models were investigated. Both temp. and pressure alter the product yields, although including pressure-dependent (chem. activated and fall-off) kinetics have minimal impact on these predictions. The model size is important, although currently constrained by available RAM, motivating development of improved memory-management algorithms in RMG. To validate the RMG-built mechanisms, simulations performed with Cantera were compared with exptl. data from the literature. Agreements and disagreements between RMG-built models and literature show that the automated mechanism generation approach is promising, but reveal some families of reactions involving heteroat. cycles that require improved ests. for bio-mass derived fuels. Research in this area would be greatly helped by more quant. exptl. data, ideally showing intermediate species profiles. These findings motivate extra studies and guide further RMG development.
- 104Han, K.; Green, W. H.; West, R. H. On-the-Fly Pruning for Rate-Based Reaction Mechanism Generation. Comput. Chem. Eng. 2017, 100, 1– 8, DOI: 10.1016/j.compchemeng.2017.01.003Google Scholar104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVGgtLw%253D&md5=b48df5ab6c5e4d5f93447f5a562f8270On-the-fly pruning for rate-based reaction mechanism generationHan, Kehang; Green, William H.; West, Richard H.Computers & Chemical Engineering (2017), 100 (), 1-8CODEN: CCENDW; ISSN:0098-1354. (Elsevier B.V.)The no. of possible side reactions and byproduct species grows very rapidly with the size of a chem. mechanism. A memory-efficient algorithm for automated mechanism generation is presented for coping with this combinatorial complexity. The algorithm selects normalized flux as a metric to identify unimportant species during model generation and prunes them with their reactions, without any loss of accuracy. The new algorithm reduces memory requirements for building kinetic models with 200-300 species by about a factor of 4, or for fixed computer hardware makes it possible to create models including about twice as many species as was previously possible. The increased capability opens the possibility of discovering unexplored reaction networks and modeling more complicated reacting systems.
- 105Dana, A. G.; Buesser, B.; Merchant, S. S.; Green, W. H. Automated Reaction Mechanism Generation Including Nitrogen as a Heteroatom. Int. J. Chem. Kinet. 2018, 50, 243– 258, DOI: 10.1002/kin.21154Google Scholar105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOqtbo%253D&md5=5ce0d70f40dea1ec2bea8cfac28998b0Automated Reaction Mechanism Generation Including Nitrogen as a HeteroatomDana, Alon Grinberg; Buesser, Beat; Merchant, Shamel S.; Green, William H.International Journal of Chemical Kinetics (2018), 50 (4), 243-258CODEN: IJCKBO; ISSN:0538-8066. (John Wiley & Sons, Inc.)The open source rate-based Reaction Mechanism Generator (RMG) software and its thermochem. and kinetics databases were extended to include nitrogen as a heteroatom. Specific changes to RMG and the mining of thermochem. and reaction kinetics data are discussed. This new version of RMG has been tested by generating a detailed pyrolysis and oxidn. model for ethylamine (EA, CH3CH2NH2) at ∼1400 K and ∼2 bar, and comparing it to recent shock tube studies. Validation of the reaction network with recent exptl. data showed that the generated model successfully reproduced the obsd. species as well as ignition delay measurements. During pyrolysis, EA initially decomps. via a C-C bond scission, and the CH2NH2 product subsequently produces the first H radicals in this system via β-scission. As the concn. of H increases, the major EA consuming reaction becomes H abstraction at the α-site by H radicals, leading to a chain reaction since its product generates more H radicals. During oxidn., the dominant N2-producing route is mediated by NO and N2O. The observables were found to be relatively sensitive to the C-C and C-N EA bond scission reactions as well as to the thermodn. values of EA; thermodn. data for EA were computed at the CBS-QB3 level and reported herein. This work demonstrates the ability of RMG to construct adequate kinetic models for nitrogenous species and discusses the pyrolysis and oxidn. mechanisms of EA.
- 106Grambow, C. A.; Jamal, A.; Li, Y.-P.; Green, W. H.; Zádor, J.; Suleimanov, Y. V. Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods. J. Am. Chem. Soc. 2018, 140, 1035– 1048, DOI: 10.1021/jacs.7b11009Google Scholar106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitVaksr%252FN&md5=cc0ce7340d7035db8729dd9cc71478d5Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery MethodsGrambow, Colin A.; Jamal, Adeel; Li, Yi-Pei; Green, William H.; Zador, Judit; Suleimanov, Yury V.Journal of the American Chemical Society (2018), 140 (3), 1035-1048CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Ketohydroperoxides are important in liq.-phase autoxidn. and in gas-phase partial oxidn. and pre-ignition chem., but because of their low concn., instability, and various anal. chem. limitations, it has been challenging to exptl. det. their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimol. reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of d. functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The present joint approach significantly outperforms previous manual and automated transition-state searches - 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chem. reactions involve promising new chem. that may be relevant in atm. and combustion systems. Our study highlights the complexity of chem. space exploration and the advantage of combined application of several approaches. Overall, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).
- 107Suleimanov, Y. V.; Green, W. H. Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization Methods. J. Chem. Theory Comput. 2015, 11, 4248, DOI: 10.1021/acs.jctc.5b00407Google Scholar107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1Srsb7I&md5=d430c76d756be29d6c52befc113e6400Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization MethodsSuleimanov, Yury V.; Green, William H.Journal of Chemical Theory and Computation (2015), 11 (9), 4248-4259CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We present a simple protocol which allows fully automated discovery of elementary chem. reaction steps using in cooperation double- and single-ended transition-state optimization algorithms - the freezing string and Berny optimization methods, resp. To demonstrate the utility of the proposed approach, the reactivity of several single-mol. systems of combustion and atm. chem. importance is investigated. The proposed algorithm allowed us to detect without any human intervention not only "known" reaction pathways, manually detected in the previous studies, but also new, previously "unknown", reaction pathways which involve significant atom rearrangements. We believe that applying such a systematic approach to elementary reaction path finding will greatly accelerate the discovery of new chem. and will lead to more accurate computer simulations of various chem. processes.
- 108Schlegel, H. B. Optimization of Equilibrium Geometries and Transition Structures. J. Comput. Chem. 1982, 3, 214– 218, DOI: 10.1002/jcc.540030212Google Scholar108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL38XktFajtrY%253D&md5=81448fcccb0620eff4b6754171e84f70Optimization of equilibrium geometries and transition structuresSchlegel, H. BernhardJournal of Computational Chemistry (1982), 3 (2), 214-18CODEN: JCCHDD; ISSN:0192-8651.A modified conjugate gradient algorithm for geometry optimization is outlined for use with ab initio MO methods. Since the computation time for anal. energy gradients is approx. the same as for the energy, the optimization algorithm evaluates and utilizes the gradients each time the energy is computed. The second deriv. matrix, rather than its inverse, is updated employing the gradients. At each step, a one-dimensional minimization using a quartic polynomial is carried out, followed by an n-dimensional search using the second deriv. matrix. By suitably controlling the no. of neg. eigenvalues of the second deriv. matrix, the algorithm can also be used to locate transition structures. Representative timeing data for optimizations of equil. geometries and transition structures are reported for ab initio SCF-MO calcns.
- 109Schlegel, H. B. Estimating the Hessian for Gradient-Type Geometry Optimizations. Theoret. Chim. Acta 1984, 66, 333– 340, DOI: 10.1007/BF00554788Google ScholarThere is no corresponding record for this reference.
- 110Peng, C.; Ayala, P. Y.; Schlegel, H. B.; Frisch, M. J. Using Redundant Internal Coordinates to Optimize Equilibrium Geometries and Transition States. J. Comput. Chem. 1996, 17, 49– 56, DOI: 10.1002/(SICI)1096-987X(19960115)17:1<49::AID-JCC5>3.0.CO;2-0Google Scholar110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XpvFSi&md5=330450a8e3f31abc94db9435cfe23935Using redundant internal coordinates to optimize equilibrium geometries and transition statesPeng, Chunyang; Ayala, Philippe; Schlegel, H. Bernhard; Frisch, Michael J.Journal of Computational Chemistry (1996), 17 (1), 49-56CODEN: JCCHDD; ISSN:0192-8651. (Wiley)A redundant internal coordinate system for optimizing mol. geometries is constructed from all bonds, all valence angles between bonded atoms, and all dihedral angles between bonded atoms. Redundancies are removed by using the generalized inverse of the G matrix; constraints can be added by using an appropriate projects. For minimizations, redundant internal coordinates provide substantial improvements in optimization efficiency over Cartesian and nonredundant internal coordinates, esp. for flexible and polycyclic systems. Transition structure searches are also improved when redundant coordinates are used and when the initial steps are guided by the quadratic synchronous transit approach.
- 111Bhoorasingh, P. L.; West, R. H. Transition State Geometry Prediction Using Molecular Group Contributions. Phys. Chem. Chem. Phys. 2015, 17, 32173– 32182, DOI: 10.1039/C5CP04706DGoogle Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFKhtb3P&md5=16e7f411e54e0417dfd07bbf66ac66b2Transition state geometry prediction using molecular group contributionsBhoorasingh, Pierre L.; West, Richard H.Physical Chemistry Chemical Physics (2015), 17 (48), 32173-32182CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Detailed kinetic models to aid the understanding of complex chem. systems require many thousands of reaction rate coeffs., most of which are estd., some quite approx. and with unknown uncertainties. This motivates the development of high-throughput methods to det. rate coeffs. via transition state theory calcns., which requires the automatic prediction of transition state (TS) geometries. We demonstrate a novel approach to predict TS geometries using a group-additive method. Distances between reactive atoms at the TS are estd. using mol. group values, with the 3D geometry of the TS being constructed by distance geometry. The est. is then optimized using electronic structure theory and validated using intrinsic reaction coordinate calcns., completing the fully automatic algorithm to locate TS geometries. The methods were tested using a diisopropyl ketone combustion model contg. 1393 hydrogen abstraction reactions, of which transition states were found for 907 over two iterations of the algorithm. With sufficient training data, mol. group contributions were shown to successfully predict the reaction center distances of transition states with root-mean-squared errors of only 0.04 Å.
- 112Rappoport, D.; Galvin, C. J.; Zubarev, D. Y.; Aspuru-Guzik, A. Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry. J. Chem. Theory Comput. 2014, 10, 897– 907, DOI: 10.1021/ct401004rGoogle Scholar112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVOqurY%253D&md5=64f81a54964e1e07a08421b61e45f495Complex Chemical Reaction Networks from Heuristics-Aided Quantum ChemistryRappoport, Dmitrij; Galvin, Cooper J.; Zubarev, Dmitry Yu.; Aspuru-Guzik, AlanJournal of Chemical Theory and Computation (2014), 10 (3), 897-907CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)While structures and reactivities of many small mols. can be computed efficiently and accurately using quantum chem. methods, heuristic approaches remain essential for modeling complex structures and large-scale chem. systems. Here, we present a heuristics-aided quantum chem. methodol. applicable to complex chem. reaction networks such as those arising in cell metab. and prebiotic chem. Chem. heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chem. structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chem. methodol. to the formose reaction reproduces the exptl. obsd. reaction products, major reaction pathways, and autocatalytic cycles.
- 113Zubarev, D. Y.; Rappoport, D.; Aspuru-Guzik, A. Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle. Sci. Rep. 2015, 5, 8009, DOI: 10.1038/srep08009Google Scholar113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXotlagsrs%253D&md5=76b8b2e61796a6a68b76dd84a9e3b45dUncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid CycleZubarev, Dmitry Yu; Rappoport, Dmitrij; Aspuru-Guzik, AlanScientific Reports (2015), 5 (), 8009/1-8009/7CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)We consider the hypothesis of the primordial nature of the non-enzymic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chem. transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.
- 114Rappoport, D.; Aspuru-Guzik, A. Predicting Feasible Organic Reaction Pathways Using Heuristically Aided Quantum Chemistry. ChemRxiv Preprint 2018, DOI: 10.26434/chemrxiv.6649565.v1Google ScholarThere is no corresponding record for this reference.
- 115Butlerow, A. Bildung einer zuckerartigen Substanz durch Synthese. Justus Liebigs Ann. Chem. 1861, 120, 295– 298, DOI: 10.1002/jlac.18611200308Google ScholarThere is no corresponding record for this reference.
- 116Levy, D. E. Arrow-Pushing in Organic Chemistry: An Easy Approach to Understanding Reaction Mechanisms, 2nd ed.; Wiley, 2017.Google ScholarThere is no corresponding record for this reference.
- 117Kim, Y.; Woo Kim, J.; Kim, Z.; Youn Kim, W. Efficient Prediction of Reaction Paths through Molecular Graph and Reaction Network Analysis. Chem. Sci. 2018, 9, 825– 835, DOI: 10.1039/C7SC03628KGoogle Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFGnsbjI&md5=71d81e16d0ac1ee7164da8f664e8dcbbEfficient prediction of reaction paths through molecular graph and reaction network analysisKim, Yeonjoon; Kim, Jin Woo; Kim, Zeehyo; Kim, Woo YounChemical Science (2018), 9 (4), 825-835CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)Despite remarkable advances in computational chem., prediction of reaction mechanisms is still challenging, because investigating all possible reaction pathways is computationally prohibitive due to the high complexity of chem. space. A feasible strategy for efficient prediction is to utilize chem. heuristics. Here, we propose a novel approach to rapidly search reaction paths in a fully automated fashion by combining chem. theory and heuristics. A key idea of our method is to ext. a minimal reaction network composed of only favorable reaction pathways from the complex chem. space through mol. graph and reaction network anal. This can be done very efficiently by exploring the routes connecting reactants and products with min. dissocn. and formation of bonds. Finally, the resulting minimal network is subjected to quantum chem. calcns. to det. kinetically the most favorable reaction path at the predictable accuracy. As example studies, our method was able to successfully find the accepted mechanisms of Claisen ester condensation and cobalt-catalyzed hydroformylation reactions.
- 118Zimmerman, P. M. Automated Discovery of Chemically Reasonable Elementary Reaction Steps. J. Comput. Chem. 2013, 34, 1385– 1392, DOI: 10.1002/jcc.23271Google Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktFWhtb4%253D&md5=443c5c1be4f67d956c120a64a77ee82dAutomated discovery of chemically reasonable elementary reaction stepsZimmerman, Paul M.Journal of Computational Chemistry (2013), 34 (16), 1385-1392CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Due to the significant human effort and chem. intuition required to locate chem. reaction pathways with quantum chem. modeling, only a small subspace of possible reactions is usually studied for any given system. Herein, a systematic approach is proposed for locating reaction paths that bypasses the required human effort and expands the reactive search space, all while maintaining low computational cost. To achieve this, a range of intermediates are generated that represent potential single elementary steps away from a starting structure. These structures are then screened to identify those that are thermodynamically accessible, and then feasible reaction paths to the remaining structures are located. This strategy for elementary reaction path finding is independent of atomistic model whenever bond breaking and forming are properly described. The approach is demonstrated to work well for upper main group elements, but this limitation can easily be surpassed. Further extension will allow discovery of multistep reaction mechanisms in a single computation. The method is highly parallel, allowing for effective use of modern large-scale computational clusters. © 2013 Wiley Periodicals, Inc.
- 119Zimmerman, P. M. Navigating Molecular Space for Reaction Mechanisms: An Efficient, Automated Procedure. Mol. Simul. 2015, 41, 43– 54, DOI: 10.1080/08927022.2014.894999Google Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFait7k%253D&md5=4e996b3b2f43c78843468df3e622b79aNavigating molecular space for reaction mechanisms: an efficient, automated procedureZimmerman, Paul M.Molecular Simulation (2015), 41 (1-3), 43-54CODEN: MOSIEA; ISSN:0892-7022. (Taylor & Francis Ltd.)A review; mechanism is a core chem. concept that has vital implications for reaction rate, efficiency and selectivity. The discovery of mechanism is not easy due to the great diversity of possible chem. rearrangements in even relatively simple systems. For this reason, mechanisms involving bond breaking and forming are usually proposed via chem. intuition - which limits the scope of considered possibilities - and these hypotheses are then tested using simulation or expt. This article discusses an automated simulation strategy for investigating multiple elementary step reaction mechanisms in chem. systems. The method starts from a single input structure and seeks out nearby intermediates, optimizes the proposed structures and then dets. the kinetic viability of each elementary step. The kinetically accessible intermediates are catalogued and new searches are performed on each unique structure. This process is repeated for an arbitrary no. of steps without human intervention, and massively parallel computation enables fast searches in chem. space. Importantly, this strategy can be empirically shown to lead to a finite no. of accessible structures, not a combinatorial explosion of intermediates. Therefore, the method should be able to predict multi-step reaction pathways in many interesting chem. systems. Demonstrations on org. reactions and a hydrogen storage material, ammonia borane, show that the herein proposed strategy can uncover complex reactivity without relying on existing chem. intuition.
- 120Zimmerman, P. M. Growing String Method with Interpolation and Optimization in Internal Coordinates: Method and Examples. J. Chem. Phys. 2013, 138, 184102, DOI: 10.1063/1.4804162Google Scholar120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsV2isLg%253D&md5=e315e6f2a3e4e1bf65e743d1ee3863b5Growing string method with interpolation and optimization in internal coordinates: Method and examplesZimmerman, Paul M.Journal of Chemical Physics (2013), 138 (18), 184102/1-184102/10CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The growing string method (GSM) has proven esp. useful for locating chem. reaction paths at low computational cost. While many string methods use Cartesian coordinates, these methods can be substantially improved by changes in the coordinate system used for interpolation and optimization steps. The quality of the interpolation scheme is esp. important because it dets. how close the initial path is to the optimized reaction path, and this strongly affects the rate of convergence. In this article, a detailed description of the generation of internal coordinates (ICs) suitable for use in GSM as reactive tangents and in string optimization is given. Convergence of reaction paths is smooth because the IC tangent and orthogonal directions are better representations of chem. bonding compared to Cartesian coordinates. This is not only important quant. for reducing computational cost but also allows reaction paths to be described with smoothly varying chem. relevant coordinates. Benchmark computations with challenging reactions are compared to previous versions of GSM and show significant speedups. Finally, a climbing image scheme is included to improve the quality of the transition state approxn., ensuring high reliability of the method. (c) 2013 American Institute of Physics.
- 121Zimmerman, P. M. Single-Ended Transition State Finding with the Growing String Method. J. Comput. Chem. 2015, 36, 601– 611, DOI: 10.1002/jcc.23833Google Scholar121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXltVKlsQ%253D%253D&md5=4b3087ccfd79ea3fba13820a2be013e3Single-ended transition state finding with the growing string methodZimmerman, Paul M.Journal of Computational Chemistry (2015), 36 (9), 601-611CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Reaction path finding and transition state (TS) searching are important tasks in computational chem. Methods that seek to optimize an evenly distributed set of structures to represent a chem. reaction path are known as double-ended string methods. Such methods can be highly reliable because the endpoints of the string are fixed, which effectively lowers the dimensionality of the reaction path search. String methods, however, require that the reactant and product structures are known beforehand, which limits their ability for systematic exploration of reactive steps. In this article, a single-ended growing string method (GSM) is introduced which allows for reaction path searches starting from a single structure. The method works by sequentially adding nodes along coordinates that drive bonds, angles, and/or torsions to a desired reactive outcome. After the string is grown and an approx. reaction path through the TS is found, string optimization commences and the exact TS is located along with the reaction path. Fast convergence of the string is achieved through use of internal coordinates and eigenvector optimization schemes combined with Hessian ests. Comparison to the double-ended GSM shows that single-ended method can be even more computationally efficient than the already rapid double-ended method. Examples, including transition metal reactivity and a systematic, automated search for unknown reactivity, demonstrate the efficacy of the new method. This automated reaction search is able to find 165 reaction paths from 333 searches for the reaction of NH3BH3 and (LiH)4, all without guidance from user intuition. © 2015 Wiley Periodicals, Inc.
- 122Jafari, M.; Zimmerman, P. M. Reliable and Efficient Reaction Path and Transition State Finding for Surface Reactions with the Growing String Method. J. Comput. Chem. 2017, 38, 645– 658, DOI: 10.1002/jcc.24720Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslSju74%253D&md5=a8441a251705eefd13a4c844ad88da74Reliable and efficient reaction path and transition state finding for surface reactions with the growing string methodJafari, Mina; Zimmerman, Paul M.Journal of Computational Chemistry (2017), 38 (10), 645-658CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)The computational challenge of fast and reliable transition state and reaction path optimization requires new methodol. strategies to maintain low cost, high accuracy, and systematic searching capabilities. The growing string method using internal coordinates has proven to be highly effective for the study of mol., gas phase reactions, but difficulties in choosing a suitable coordinate system for periodic systems has prevented its use for surface chem. New developments are therefore needed, and presented herein, to handle surface reactions which include atoms with large coordination nos. that cannot be treated using std. internal coordinates. The double-ended and single-ended growing string methods are implemented using a hybrid coordinate system, then benchmarked for a test set of 43 elementary reactions occurring on surfaces. These results show that the growing string method is at least 45% faster than the widely used climbing image-nudged elastic band method, which also fails to converge in several of the test cases. Addnl., the surface growing string method has a unique single-ended search method which can move outward from an initial structure to find the intermediates, transition states, and reaction paths simultaneously. This powerful explorative feature of single ended-growing string method is demonstrated to uncover, for the first time, the mechanism for at. layer deposition of TiN on Cu(111) surface. This reaction is found to proceed through multiple hydrogen-transfer and ligand-exchange events, while formation of H-bonds stabilizes intermediates of the reaction. Purging gaseous products out of the reaction environment is the driving force for these reactions. © 2017 Wiley Periodicals, Inc.
- 123Nett, A. J.; Zhao, W.; Zimmerman, P. M.; Montgomery, J. Highly Active Nickel Catalysts for C–H Functionalization Identified through Analysis of Off-Cycle Intermediates. J. Am. Chem. Soc. 2015, 137, 7636– 7639, DOI: 10.1021/jacs.5b04548Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVansLzJ&md5=a505b5a761d3a525a26dbb20f9b815e9Highly Active Nickel Catalysts for C-H Functionalization Identified through Analysis of Off-Cycle IntermediatesNett, Alex J.; Zhao, Wanxiang; Zimmerman, Paul M.; Montgomery, JohnJournal of the American Chemical Society (2015), 137 (24), 7636-7639CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An inhibitory role of 1,5-cyclooctadiene (COD) in nickel-catalyzed C-H functionalization processes was identified and studied. The bound COD participates in C-H activation by capturing the hydride, leading to a stable off-cycle π-allyl complex that greatly diminished overall catalytic efficiency. Computational studies elucidated the origin of the effect and enabled identification of a 1,5-hexadiene-derived pre-catalyst that avoids the off-cycle intermediate and provides catalytic efficiencies that are superior to those of catalysts derived from Ni(COD)2.
- 124Li, M. W.; Pendleton, I. M.; Nett, A. J.; Zimmerman, P. M. Mechanism for Forming B,C,N,O Rings from NH3BH3and vCO2ia Reaction Discovery Computations. J. Phys. Chem. A 2016, 120, 1135– 1144, DOI: 10.1021/acs.jpca.5b11156Google ScholarThere is no corresponding record for this reference.
- 125Pendleton, I. M.; Pérez-Temprano, M. H.; Sanford, M. S.; Zimmerman, P. M. Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)–N Bond-Forming Reductive Elimination from Palladium(IV). J. Am. Chem. Soc. 2016, 138, 6049– 6060, DOI: 10.1021/jacs.6b02714Google Scholar125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtF2murk%253D&md5=f739ebd816c70d6b9930b82153ca7aa7Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)-N Bond-Forming Reductive Elimination from Palladium(IV)Pendleton, Ian M.; Perez-Temprano, Monica H.; Sanford, Melanie S.; Zimmerman, Paul M.Journal of the American Chemical Society (2016), 138 (18), 6049-6060CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)This report describes a combined exptl. and computational investigation of the mechanism of C(sp3)-N bond-forming reductive elimination from sulfonamide-ligated PdIV complexes. After an initial exptl. assessment of reactivity, we used ZStruct, a computational combinatorial reaction finding method, to analyze a large no. of multistep mechanisms for this process. This study reveals two facile isomerization pathways connecting the exptl. obsd. PdIV isomers, along with two competing SN2 pathways for C(sp3)-N coupling. One of these pathways involves an unanticipated oxygen-nitrogen exchange of the sulfonamide ligand prior to an inner-sphere SN2-type reductive elimination. The calcd. ΔG⧺ values for isomerization and reductive elimination with a series of sulfonamide derivs. are in good agreement with exptl. data. Furthermore, the simulations predict relative reaction rates with different sulfonamides, which is successful only after considering competition between the proposed operating mechanisms. Overall, this work shows that the combination of exptl. studies and new computational tools can provide fundamental mechanistic insights into complex organometallic reaction pathways.
- 126Zhao, Y.; Nett, A. J.; McNeil, A. J.; Zimmerman, P. M. Computational Mechanism for Initiation and Growth of Poly(3-Hexylthiophene) Using Palladium N-Heterocyclic Carbene Precatalysts. Macromolecules 2016, 49, 7632– 7641, DOI: 10.1021/acs.macromol.6b01648Google ScholarThere is no corresponding record for this reference.
- 127Dewyer, A. L.; Zimmerman, P. M. Finding Reaction Mechanisms, Intuitive or Otherwise. Org. Biomol. Chem. 2017, 15, 501– 504, DOI: 10.1039/C6OB02183BGoogle Scholar127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVyjtbjJ&md5=1f70486f3755a036f7a878bbf98bc52bFinding reaction mechanisms, intuitive or otherwiseDewyer, Amanda L.; Zimmerman, Paul M.Organic & Biomolecular Chemistry (2017), 15 (3), 501-504CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)Chem. reaction mechanisms have been frequently studied using computational simulations, but these tools have been primarily effective at examg. reaction paths within the scope of chem. intuition. To det. reaction mechanisms that were not already preconceived by chemists, nonstandard simulation tools are required. This perspective introduces new methods developed by the Zimmerman group that are designed to uncover sequences of elementary steps, from first principles and without substantial human guidance. Results from the areas of organo catalysis and transition metal catalysis indicate that new frontiers of knowledge will be gained through continued development and application of reaction discovery simulation techniques.
- 128Ludwig, J. R.; Zimmerman, P. M.; Gianino, J. B.; Schindler, C. S. Iron(III)-Catalysed Carbonyl–Olefin Metathesis. Nature 2016, 533, 374– 379, DOI: 10.1038/nature17432Google Scholar128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmvVGntrY%253D&md5=4763c79022c8121eef0dc857214954dbIron(III)-catalysed carbonyl-olefin metathesisLudwig, Jacob R.; Zimmerman, Paul M.; Gianino, Joseph B.; Schindler, Corinna S.Nature (London, United Kingdom) (2016), 533 (7603), 374-379CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The olefin metathesis reaction of two unsatd. substrates is one of the most powerful carbon-carbon-bond-forming reactions in org. chem. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of mols. relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
- 129Smith, M. L.; Leone, A. K.; Zimmerman, P. M.; McNeil, A. J. Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole Derivatives. ACS Macro Lett. 2016, 5, 1411– 1415, DOI: 10.1021/acsmacrolett.6b00886Google Scholar129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVejsLbP&md5=ecff32183eb4d751c490869b57211ab3Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole DerivativesSmith, Mitchell L.; Leone, Amanda K.; Zimmerman, Paul M.; McNeil, Anne J.ACS Macro Letters (2016), 5 (12), 1411-1415CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Polymg. electron-deficient arenes in a controlled, chain-growth fashion remains a significant challenge despite a decade of research on catalyst-transfer polycondensation. The prevailing hypothesis is that the chain-growth mechanism stalls at a strongly assocd. metal-polymer π-complex, preventing catalyst turnover. To evaluate this hypothesis, we performed mechanistic studies using thiazole derivs. and identified approaches to improve their chain-growth polymn. These studies revealed a surprisingly high barrier for chain-walking toward the reactive C-X bond. In addn., a competitive pathway involving chain-transfer to monomer was identified. This pathway is facilitated by ancillary ligand dissocn. and N-coordination to the incoming monomer. We found that this chain-transfer pathway can be attenuated by using a rigid ancillary ligand, leading to an improved polymn. Combined, these studies provide mechanistic insight into the challenges assocd. with electron-deficient monomers and ways to improve their living, chain-growth polymn. Our mechanistic studies also revealed an unexpected radical anion-mediated oligomerization in the absence of catalyst, and a surprising oxidative addn. into the thiazole C-S bond in a model system.
- 130Ludwig, J. R.; Phan, S.; McAtee, C. C.; Zimmerman, P. M.; Devery, J. J.; Schindler, C. S. Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis Reaction. J. Am. Chem. Soc. 2017, 139, 10832– 10842, DOI: 10.1021/jacs.7b05641Google Scholar130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1egt7jM&md5=4a6fef8b15abcdf907ae50c6cfda4874Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis ReactionLudwig, Jacob R.; Phan, Susan; McAtee, Christopher C.; Zimmerman, Paul M.; Devery, James J., III; Schindler, Corinna S.Journal of the American Chemical Society (2017), 139 (31), 10832-10842CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new approach toward the assembly of mols. traditionally generated by olefin-olefin metathesis or olefination. Herein, we report detailed synthetic, spectroscopic, kinetic, and computational studies to det. the mechanistic features imparted by iron(III), substrate, and temp. to the catalytic cycle. These data are consistent with an iron(III)-mediated asynchronous, concerted [2+2]-cycloaddn. to form an intermediate oxetane as the turnover-limiting step. Fragmentation of the oxetane via Lewis acid-activation results in the formation of five- and six-membered unsatd. carbocycles.
- 131Dewyer, A. L.; Zimmerman, P. M. Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of Piperidine. ACS Catal. 2017, 7, 5466– 5477, DOI: 10.1021/acscatal.7b01390Google Scholar131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1SjtrrL&md5=6411ffbbfdd8b838027c426c5c1ca207Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of PiperidineDewyer, Amanda L.; Zimmerman, Paul M.ACS Catalysis (2017), 7 (8), 5466-5477CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Quantum chem. reaction path finding methods are herein used to investigate the mechanism of Pd-catalyzed distal functionalization of piperidine, as reported by Sanford. These methods allowed navigation of a complex reaction landscape with multiple reactants interacting at all key steps of the proposed catalytic cycle. A multistep cycle is shown to conceptually begin with substrate ligation and Pd(II)-catalyzed C-H activation, which occurs through concerted metalation-deprotonation. In subsequent steps, the kinetic and thermodn. profiles for oxidative addn., reductive elimination, and catalyst regeneration show why excess Cs salts and ArI were required in the expt. Specifically, excess ArI is necessary to thermodynamically overcome the high energy of the C-H activated intermediate and allow oxidative addn. to be favorable, and excess Cs salt is needed to sequester reaction byproducts during oxidative addn. and catalyst regeneration. The overall catalytic profile is consistent with rate-limiting C-H activation, explains the probable functions of all major exptl. conditions, and gives atomistic detail to guide expt. to improve this challenging transformation even further.
- 132Habershon, S. Sampling Reactive Pathways with Random Walks in Chemical Space: Applications to Molecular Dissociation and Catalysis. J. Chem. Phys. 2015, 143, 094106, DOI: 10.1063/1.4929992Google Scholar132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVCms73P&md5=10d9945d033f6fcbdf91a9a4859d4243Sampling reactive pathways with random walks in chemical space: Applications to molecular dissociation and catalysisHabershon, ScottJournal of Chemical Physics (2015), 143 (9), 094106/1-094106/14CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Automatically generating chem. reaction pathways is a significant computational challenge, particularly in the case where a given chem. system can exhibit multiple reactants and products, as well as multiple pathways connecting these. Here, we outline a computational approach to allow automated sampling of chem. reaction pathways, including sampling of different chem. species at the reaction end-points. The key features of this scheme are (i) introduction of a Hamiltonian which describes a reaction "string" connecting reactant and products, (ii) definition of reactant and product species as chem. connectivity graphs, and (iii) development of a scheme for updating the chem. graphs assocd. with the reaction end-points. By performing mol. dynamics sampling of the Hamiltonian describing the complete reaction pathway, we are able to sample multiple different paths in configuration space between given chem. products; by periodically modifying the connectivity graphs describing the chem. identities of the end-points we are also able to sample the allowed chem. space of the system. Overall, this scheme therefore provides a route to automated generation of a "roadmap" describing chem. reactivity. This approach is first applied to model dissocn. pathways in formaldehyde, H2CO, as described by a parameterised potential energy surface (PES). A second application to the HCo(CO)3 catalyzed hydroformylation of ethene (oxo process), using d. functional tight-binding to model the PES, demonstrates that our graph-based approach is capable of sampling the intermediate paths in the commonly accepted catalytic mechanism, as well as several secondary reactions. Further algorithmic improvements are suggested which will pave the way for treating complex multi-step reaction processes in a more efficient manner. (c) 2015 American Institute of Physics.
- 133Habershon, S. Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path Sampling. J. Chem. Theory Comput. 2016, 12, 1786– 1798, DOI: 10.1021/acs.jctc.6b00005Google Scholar133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs1Sqtbk%253D&md5=f227bc5d2e1be8e62e71c72bf772bb71Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path SamplingHabershon, ScottJournal of Chemical Theory and Computation (2016), 12 (4), 1786-1798CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In a recent article [ J. Chem. Phys. 2015, 143, 094106], we introduced a novel graph-based sampling scheme which can be used to generate chem. reaction paths in many-atom systems in an efficient and highly automated manner. The main goal of this work is to demonstrate how this approach, when combined with direct kinetic modeling, can be used to det. the mechanism and phenomenol. rate law of a complex catalytic cycle, namely cobalt-catalyzed hydroformylation of ethene. Our graph-based sampling scheme generates 31 unique chem. products and 32 unique chem. reaction pathways; these sampled structures and reaction paths enable automated construction of a kinetic network model of the catalytic system when combined with d. functional theory (DFT) calcns. of free energies and resultant transition-state theory rate consts. Direct simulations of this kinetic network across a range of initial reactant concns. enables detn. of both the reaction mechanism and the assocd. rate law in an automated fashion, without the need for either presupposing a mechanism or making steady-state approxns. in kinetic anal. Most importantly, we find that the reaction mechanism which emerges from these simulations is exactly that originally proposed by Heck and Breslow; furthermore, the simulated rate law is also consistent with previous exptl. and computational studies, exhibiting a complex dependence on carbon monoxide pressure. While the inherent errors of using DFT simulations to model chem. reactivity limit the quant. accuracy of our calcd. rates, this work confirms that our automated simulation strategy enables direct anal. of catalytic mechanisms from first principles.
- 134Wheeler, S. E.; Seguin, T. J.; Guan, Y.; Doney, A. C. Noncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst Design. Acc. Chem. Res. 2016, 49, 1061– 1069, DOI: 10.1021/acs.accounts.6b00096Google Scholar134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmsFCrsLw%253D&md5=4cffcbf91f93ae4ecaf20537c364fcebNoncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst DesignWheeler, Steven E.; Seguin, Trevor J.; Guan, Yanfei; Doney, Analise C.Accounts of Chemical Research (2016), 49 (5), 1061-1069CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Noncovalent interactions are ubiquitous in org. systems, and can play decisive roles in the outcome of asym. organocatalytic reactions. Their prevalence, combined with the often subtle line sepg. favorable dispersion interactions from unfavorable steric interactions, often complicates the identification of the particular noncovalent interactions responsible for stereoselectivity. Ultimately, the stereoselectivity of most organocatalytic reactions hinges on the balance of both favorable and unfavorable noncovalent interactions in the stereocontrolling transition state (TS). In this Account, we provide an overview of our attempts to understand the role of noncovalent interactions in organocatalyzed reactions and to develop new computational tools for organocatalyst design. Following a brief discussion of noncovalent interactions involving arom. rings and the assocd. challenges capturing these effects computationally, we summarize two examples of chiral phosphoric acid catalyzed reactions in which noncovalent interactions play pivotal, although somewhat unexpected, roles. In the first, List's catalytic asym. Fischer indole reaction, we show that both π-stacking and CH/π interactions of the substrate with the 3,3'-aryl groups of the catalyst impact the stability of the stereocontrolling TS. However, these noncovalent interactions oppose each other, with π-stacking interactions stabilizing the TS leading to one enantiomer and CH/π interactions preferentially stabilizing the competing TS. Ultimately, the CH/π interactions dominate and, when combined with hydrogen bonding interactions, lead to preferential formation of the obsd. product. In the second example, a series of phosphoric acid catalyzed asym. ring openings of meso-epoxides, we show that noncovalent interactions of the substrates with the 3,3'-aryl groups of the catalyst play only an indirect role in stereoselectivity. Instead, the stereoselectivity of these reactions are driven by the electrostatic stabilization of a fleeting partial pos. charge in the SN2-like transition state by the chiral electrostatic environment of the phosphoric acid catalyst. Next, we describe our studies of bipyridine N-oxide and N,N'-dioxide catalyzed alkylation reactions. Based on several examples, we demonstrate that there are many potential arrangements of ligands around a hexacoordinate silicon in the stereocontrolling TS, and one must consider all of these in order to identify the lowest-lying TS structures. We also present a model in which electrostatic interactions between a formyl CH group and a chlorine in these TSs underlie the enantioselectivity of these reactions. Finally, we discuss our efforts to develop computational tools for the screening of potential organocatalyst designs, starting in the context of bipyridine N,N'-dioxide catalyzed alkylation reactions. Our new computational tool kit (AARON) has been used to design highly effective catalysts for the asym. propargylation of benzaldehyde, and is currently being used to screen catalysts for other reactions. We conclude with our views on the potential roles of computational chem. in the future of organocatalyst design.
- 135Doney, A. C.; Rooks, B. J.; Lu, T.; Wheeler, S. E. Design of Organocatalysts for Asymmetric Propargylations through Computational Screening. ACS Catal. 2016, 6, 7948– 7955, DOI: 10.1021/acscatal.6b02366Google Scholar135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yks7jO&md5=207d00d90bba03b6dfeed14f3762364aDesign of Organocatalysts for Asymmetric Propargylations through Computational ScreeningDoney, Analise C.; Rooks, Benjamin J.; Lu, Tongxiang; Wheeler, Steven E.ACS Catalysis (2016), 6 (11), 7948-7955CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)The development of asym. catalysts is typically driven by the exptl. screening of potential catalyst designs. Herein, the authors demonstrate the design of asym. propargylation catalysts through computational screening. This was done using computational toolkit AARON (automated alkylation reaction optimizer for N-oxides), which automates the prediction of enantioselectivities for bidentate Lewis base catalyzed alkylation reactions. A systematic screening of 59 potential catalysts built on 6 bipyridine N,N'-dioxide-derived scaffolds results in predicted ee values for the propargylation of benzaldehyde ranging from 45% (S) to 99% (R), with 12 ee values exceeding 95%. These data provide a broad set of exptl. testable predictions. Also, the assocd. data revealed key details regarding the role of stabilizing electrostatic interactions in asym. propargylations, which were harnessed in the design of a propargylation catalyst for which the predicted ee exceeds 99%.
- 136Guan, Y.; Wheeler, S. E. Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium-Catalyzed Asymmetric Hydrogenation. Angew. Chem. 2017, 129, 9229– 9233, DOI: 10.1002/ange.201704663Google ScholarThere is no corresponding record for this reference.
- 137Guan, Y.; Ingman, V. M.; Rooks, B. J.; Wheeler, S. E. AARON: An Automated Reaction Optimizer for New Catalysts. J. Chem. Theory Comput. 2018, 14, 5249, DOI: 10.1021/acs.jctc.8b00578Google Scholar137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVOlsbbO&md5=f8e15c28a5e202415fbb232e93310a79AARON: An Automated Reaction Optimizer for New CatalystsGuan, Yanfei; Ingman, Victoria M.; Rooks, Benjamin J.; Wheeler, Steven E.Journal of Chemical Theory and Computation (2018), 14 (10), 5249-5261CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe an open-source computational toolkit (AARON: An Automated Reaction Optimizer for New catalysts) that automates the quantum mech. geometry optimization and characterization of the transition state and intermediate structures required to predict the activities and selectivities of asym. catalytic reactions. Modern computational quantum chem. has emerged as a powerful tool for explaining the selectivity and activity of asym. catalysts. However, reliably predicting the stereochem. outcome of realistic reactions often requires the geometry optimization of hundreds of transition state and intermediate structures, which is a tedious process. AARON automates these optimizations through an interface with a popular electronic structure package, accelerating quantum chem. workflows to enable the computational screening of potential catalysts. AARON is built using a collection of object-oriented Perl modules (AaronTools) that provide functionality to build and modify mol. and supramol. structures. The main functionalities of AaronTools are also available as stand-alone command-line scripts. The core features of AaronTools and AARON are explained, and representative applications of AARON to both organocatalyzed and transition-metal-catalyzed reactions are presented.
- 138Geerlings, P.; De Proft, F.; Langenaeker, W. Conceptual Density Functional Theory. Chem. Rev. 2003, 103, 1793– 1874, DOI: 10.1021/cr990029pGoogle Scholar138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXivFGgu7g%253D&md5=085c8ae5893c0b05158629e182ecb0a4Conceptual Density Functional TheoryGeerlings, P.; De Proft, F.; Langenaeker, W.Chemical Reviews (Washington, DC, United States) (2003), 103 (5), 1793-1873CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on conceptual d. functional theory including the following topics: fundamental and computational aspects of DFT, DFT-based concepts and principles and applications of DFT.
- 139Geerlings, P.; Proft, F. D. Conceptual DFT: The Chemical Relevance of Higher Response Functions. Phys. Chem. Chem. Phys. 2008, 10, 3028– 3042, DOI: 10.1039/b717671fGoogle Scholar139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVKmt7o%253D&md5=d0abd6b5a14679da7da2cef53918a636Conceptual DFT: the chemical relevance of higher response functionsGeerlings, P.; De Proft, F.Physical Chemistry Chemical Physics (2008), 10 (21), 3028-3042CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)A review. In recent years conceptual d. functional theory offered a perspective for the interpretation/prediction of exptl./theor. reactivity data on the basis of a series of response functions to perturbations in the no. of electrons and/or external potential. This approach has enabled the sharp definition and computation, from first principles, of a series of well-known but sometimes vaguely defined chem. concepts such as electronegativity and hardness. In this contribution, a short overview of the shortcomings of the simplest, first-order response functions is illustrated leading to a description of chem. bonding in a covalent interaction in terms of interacting atoms or groups, governed by electrostatics with the tendency to polarize bonds on the basis of electronegativity differences. The second order approach, well known until now, introduces the hardness/softness and Fukui function concepts related to polarizability and frontier MO theory, resp. The introduction of polarizability/softness is also considered in a historical perspective in which polarizability was, with some exceptions, mainly put forward in non covalent interactions. A particular series of response functions, arising when the changes in the external potential are solely provoked by changes in nuclear configurations (the "R-analogs") are also systematically considered. The main part of the contribution is devoted to third-order response functions which, at first sight, may be expected not to yield chem. significant information, as turns out to be for the hyperhardness. A counterexample is the dual descriptor and its R analog, the initial hardness response, which turns out to yield a firm basis to regain the Woodward-Hoffmann rules for pericyclic reactions based on a d.-only basis, i.e. without involving the phase, sign, symmetry of the wavefunction. Even the second-order nonlinear response functions are shown possibly to bear interesting information, e.g. on the local and global polarizability. Its derivs. may govern the influence of charge on the polarizability, the R-analogs being the nuclear Fukui function and the quadratic and cubic force consts. Although some of the higher order derivs. may be difficult to evaluate a comparison with the energy expansion used in spectroscopy in terms of nuclear displacements, nuclear magnetic moments, elec. and magnetic fields leads to the conjecture that, certainly cross terms may contain new, intricate information for understanding chem. reactivity.
- 140Proft, F. D.; Ayers, P. W.; Geerlings, P. The Chemical Bond; Wiley-Blackwell, 2014; pp 233– 270.Google ScholarThere is no corresponding record for this reference.
- 141Bergeler, M.; Simm, G. N.; Proppe, J.; Reiher, M. Heuristics-Guided Exploration of Reaction Mechanisms. J. Chem. Theory Comput. 2015, 11, 5712– 5722, DOI: 10.1021/acs.jctc.5b00866Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslCjtbjO&md5=c283427244c99d448f5c895d6f434b06Heuristics-Guided Exploration of Reaction MechanismsBergeler, Maike; Simm, Gregor N.; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2015), 11 (12), 5712-5722CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For the investigation of chem. reaction networks, the efficient and accurate detn. of all relevant intermediates and elementary reactions is mandatory. The complexity of such a network may grow rapidly, in particular if reactive species are involved that might cause a myriad of side reactions. Without automation, a complete investigation of complex reaction mechanisms is tedious and possibly unfeasible. Therefore, only the expected dominant reaction paths of a chem. reaction network (e.g., a catalytic cycle or an enzymic cascade) are usually explored in practice. Here, we present a computational protocol that constructs such networks in a parallelized and automated manner. Mol. structures of reactive complexes are generated based on heuristic rules derived from conceptual electronic-structure theory and subsequently optimized by quantum-chem. methods to produce stable intermediates of an emerging reaction network. Pairs of intermediates in this network that might be related by an elementary reaction according to some structural similarity measure are then automatically detected and subjected to an automated search for the connecting transition state. The results are visualized as an automatically generated network graph, from which a comprehensive picture of the mechanism of a complex chem. process can be obtained that greatly facilitates the anal. of the whole network. We apply our protocol to the Schrock dinitrogen-fixation catalyst to study alternative pathways of catalytic ammonia prodn.
- 142Gánti, T. Organization of Chemical Reactions into Dividing and Metabolizing Units: The Chemotons. BioSystems 1975, 7, 15– 21, DOI: 10.1016/0303-2647(75)90038-6Google ScholarThere is no corresponding record for this reference.
- 143Yandulov, D. V.; Schrock, R. R. Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine Complex. J. Am. Chem. Soc. 2002, 124, 6252– 6253, DOI: 10.1021/ja020186xGoogle Scholar143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XjsVyhsb8%253D&md5=5a7abc5e8c8135193ceb83918f21ea43Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine ComplexYandulov, Dmitry V.; Schrock, Richard R.Journal of the American Chemical Society (2002), 124 (22), 6252-6253CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We have synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (HexaIsoPropylTerphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 led to formation of orange [HIPTN3N]MoCl. Redn. of [HIPTN3N]MoCl with magnesium in THF under dinitrogen led to formation of salts that contain the {[HIPTN3N]Mo(N2)}- ion. The {[HIPTN3N]Mo(N2)}- ion can be oxidized by zinc chloride to give [HIPTN3N]Mo(N2) or protonated to give [HIPTN3N]Mo-N:N-H. Other relevant compds. that have been prepd. include {[HIPTN3N]Mo-N:NH2}+, [HIPTN3N]Mo≡N, {[HIPTN3N]Mo:NH}+, and {[HIPTN3N]Mo(NH3)}+. (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-.). Redn. of [HIPTN3N]Mo(N2) with CoCp2 in the presence of {2,6-lutidinium}BAr'4 in benzene leads to formation of ammonia and {[HIPTN3N]Mo(NH3)}+. Preliminary X-ray studies suggest that the HIPT substituent creates a deep, three-fold sym. cavity that protects a variety of dinitrogen redn. products against bimol. decompn. reactions, while at the same time the metal is left relatively open toward reactions near the equatorial amido ligands.
- 144Yandulov, D. V.; Schrock, R. R.; Rheingold, A. L.; Ceccarelli, C.; Davis, W. M. Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl Substituents. Inorg. Chem. 2003, 42, 796– 813, DOI: 10.1021/ic020505lGoogle Scholar144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjt1yqtg%253D%253D&md5=224f2e5ebc46cf53c66ce1e68f6de311Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl SubstituentsYandulov, Dmitry V.; Schrock, Richard R.; Rheingold, Arnold L.; Ceccarelli, Christopher; Davis, William M.Inorganic Chemistry (2003), 42 (3), 796-813CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)The authors synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (hexaisopropylterphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 gave orange [HIPTN3N]MoCl. Redn. of MoCl (Mo = [HIPTN3N]Mo) with Mg in THF under dinitrogen gave salts that contain the {Mo(N2)}- ion. The {Mo(N2)}- ion can be oxidized by ZnCl2 to give Mo(N2) or protonated to give MoN:NH. The latter decomps. to yield MoH. Other relevant compds. that were prepd. include {Mo:N-NH2}+ (by protonation of MoN:NH), Mo≡N, {Mo=NH}+ (by protonation of Mo≡N), and {Mo(NH3)}+ (by treating MoCl with NH3) (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-). X-ray studies were carried out on {Mg(DME)3}0.5[Mo(N2)], MoN:NMgBr(THF)3, Mo(N2), Mo≡N, and {Mo(NH3)}{BAr'4}. Probably the HIPT substituent on the triamidoamine ligand creates a cavity that stabilizes a variety of complexes that might be encountered in a hypothetical Chatt-like dinitrogen redn. scheme, perhaps largely by protecting against bimol. decompn. reactions.
- 145Eschenmoser, A.; Loewenthal, E. Chemistry of Potentially Prebiological Natural Products. Chem. Soc. Rev. 1992, 21, 1– 16, DOI: 10.1039/cs9922100001Google Scholar145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38Xht1egtL4%253D&md5=26e2c8a468693ecdbff4a3b01d3766beChemistry of potentially prebiological natural productsEschenmoser, Albert; Loewenthal, EliChemical Society Reviews (1992), 21 (1), 1-16CODEN: CSRVBR; ISSN:0306-0012.A review with 59 refs. on the title subject with regard to sugar phosphates, purines, pyrimidines and oligonucleotides.
- 146Delidovich, I. V.; Simonov, A. N.; Taran, O. P.; Parmon, V. N. Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis. ChemSusChem 2014, 7, 1833– 1846, DOI: 10.1002/cssc.201400040Google Scholar146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslGjtLw%253D&md5=3f51d7aa82ef147a6e790097a698e7c5Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective SynthesisDelidovich, Irina V.; Simonov, Alexandr N.; Taran, Oxana P.; Parmon, Valentin N.ChemSusChem (2014), 7 (7), 1833-1846CODEN: CHEMIZ; ISSN:1864-5631. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The formose reaction (FR) was long the focus of intensive studies as a simple method for synthesis of complex biol. important monosaccharides and other sugar-like mols. from the simplest org. substrate-formaldehyde. The fundamental importance of the FR is predominantly connected with the ascertainment of plausible scenarios of chem. evolution which could occurred on the prebiotic Earth to produce the very first mols. of carbohydrates, amino- and nucleic acids, as well as other vitally important substances. The practical importance of studies on the FR is the elaboration of catalytic methods for the synthesis of rare and nonnatural monosaccharides and polyols. This Minireview considers the FR from the point of view of chemists working in the field of catalysis with emphasis on the mechanisms of numerous parallel and consequent catalytic transformations that take place during the FR. Based on its kinetics, the FR may be considered as a nonradical chain process with degenerate branching. The Minireview also considers different approaches to the control of selectivity of carbohydrate synthesis from formaldehyde and lower monosaccharides.
- 147Simm, G. N.; Reiher, M. Context-Driven Exploration of Complex Chemical Reaction Networks. J. Chem. Theory Comput. 2017, 13, 6108– 6119, DOI: 10.1021/acs.jctc.7b00945Google Scholar147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsleiurfJ&md5=1a898dab5d04f2c4889afb549a4dbb5aContext-Driven Exploration of Complex Chemical Reaction NetworksSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (12), 6108-6119CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The construction of a reaction network contg. all relevant intermediates and elementary reactions is necessary for the accurate description of chem. processes. In the case of a complex chem. reaction (involving, for instance, many reactants or highly reactive species), the size of such a network may grow rapidly. Here, we present a computational protocol that constructs such reaction networks in a fully automated fashion steered in an intuitive, graph-based fashion through a single graphical user interface. Starting from a set of initial reagents new intermediates are explored through intra- and intermol. reactions of already explored intermediates or new reactants presented to the network. This is done by assembling reactive complexes based on heuristic rules derived from conceptual electronic-structure theory and exploring the corresponding approx. reaction path. A subsequent path refinement leads to a min.-energy path which connects the new intermediate to the existing ones to form a connected reaction network. Tree traversal algorithms are then employed to detect reaction channels and catalytic cycles. We apply our protocol to the formose reaction to study different pathways of sugar formation and to rationalize its autocatalytic nature.
- 148Proppe, J.; Reiher, M. Mechanism Deduction from Noisy Chemical Reaction Networks. J. Chem. Theory Comput. 2018, submitted, [arXiv: 1803.09346].Google ScholarThere is no corresponding record for this reference.
- 149Husch, T.; Vaucher, A. C.; Reiher, M. Semiempirical Molecular Orbital Models based on the Neglect of Diatomic Differential Overlap Approximation. Int. J. Quantum Chem. 2018, e25799 DOI: 10.1002/qua.25799Google ScholarThere is no corresponding record for this reference.
- 150Husch, T.; Reiher, M. Comprehensive analysis of the neglect of diatomic differential overlap approximation. J. Chem. Theory Comput. 2018, 14, 5169– 5179, DOI: 10.1021/acs.jctc.8b00601Google Scholar150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1KhtbzI&md5=1410f3e6922bfcc2d97eb12e6ebbb005Comprehensive Analysis of the Neglect of Diatomic Differential Overlap ApproximationHusch, Tamara; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5169-5179CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Many modern semiempirical MO models are built on the NDDO approxn. An in-depth understanding of this approxn. is therefore indispensable to rationalize the success of these semiempirical MO models and to develop further improvements on them. The NDDO approxn. provides a recipe to approx. electron-electron repulsion integrals (ERIs) in a sym. orthogonalized basis based on a far smaller no. of ERIs in a locally orthogonalized basis. We first analyze the NDDO approxn. by comparing ERIs in both bases for a selection of mols. and for a selection of basis sets. We find that the errors in Hartree-Fock and second-order Moller-Plesset perturbation theory energies grow roughly linearly with the no. of basis functions. We then examine different approaches to correct for the errors caused by the NDDO approxn. and propose a strategy to directly correct for them in the two-electron matrixes that enter the Fock operator.
- 151Simm, G. N.; Proppe, J.; Reiher, M. Error Assessment of Computational Models in Chemistry. Chimia 2017, 71, 202– 208, DOI: 10.2533/chimia.2017.202Google Scholar151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1ajt7rK&md5=88488125dbc1ae5214a8b22d52d9570bError assessment of computational models in chemistrySimm, Gregor N.; Proppe, Jonny; Reiher, MarkusChimia (2017), 71 (4), 202-208CODEN: CHIMAD ISSN:. (Swiss Chemical Society)Computational models in chem. rely on a no. of approxns. The effect of such approxns. on observables derived from them is often unpredictable. Therefore, it is challenging to quantify the uncertainty of a computational result, which, however, is necessary to assess the suitability of a computational model. Common performance statistics such as the mean abs. error are prone to failure as they do not distinguish the explainable (systematic) part of the errors from their unexplainable (random) part. In this paper, we discuss problems and solns. for performance assessment of computational models based on several examples from the quantum chem. literature. For this purpose, we elucidate the different sources of uncertainty, the elimination of systematic errors, and the combination of individual uncertainty components to the uncertainty of a prediction.
- 152Proppe, J.; Reiher, M. Reliable Estimation of Prediction Uncertainty for Physicochemical Property Models. J. Chem. Theory Comput. 2017, 13, 3297– 3317, DOI: 10.1021/acs.jctc.7b00235Google Scholar152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXpt1ykt7w%253D&md5=41bb917d7e3707ab9c6308a00dd056c9Reliable Estimation of Prediction Uncertainty for Physicochemical Property ModelsProppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (7), 3297-3317CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)One of the major challenges in computational science is to det. the uncertainty of a virtual measurement, that is the prediction of an observable based on calcns. As highly accurate first-principles calcns. are in general unfeasible for most phys. systems, one usually resorts to parameteric property models of observables, which require calibration by incorporating ref. data. The resulting predictions and their uncertainties are sensitive to systematic errors such as inconsistent ref. data, parametric model assumptions, or inadequate computational methods. Here, we discuss the calibration of property models in the light of bootstrapping, a sampling method that can be employed for identifying systematic errors and for reliable estn. of the prediction uncertainty. We apply bootstrapping to assess a linear property model linking the 57Fe Mossbauer isomer shift to the contact electron d. at the iron nucleus for a diverse set of 44 mol. iron compds. The contact electron d. is calcd. with 12 d. functionals across Jacob's ladder (PWLDA, BP86, BLYP, PW91, PBE, M06-L, TPSS, B3LYP, B3PW91, PBE0, M06, TPSSh). We provide systematic-error diagnostics and reliable, locally resolved uncertainties for isomer-shift predictions. Pure and hybrid d. functionals yield av. prediction uncertainties of 0.06-0.08 mm s-1 and 0.04-0.05 mm s-1, resp., the latter being close to the av. exptl. uncertainty of 0.02 mm s-1. Furthermore, we show that both model parameters and prediction uncertainty depend significantly on the compn. and no. of ref. data points. Accordingly, we suggest that rankings of d. functionals based on performance measures (e.g., the squared coeff. of correlation, r2, or the root-mean-square error, RMSE) should not be inferred from a single data set. This study presents the first statistically rigorous calibration anal. for theor. Mossbauer spectroscopy, which is of general applicability for physicochem. property models and not restricted to isomer-shift predictions. We provide the statistically meaningful ref. data set MIS39 and a new calibration of the isomer shift based on the PBE0 functional.
- 153Weymuth, T.; Proppe, J.; Reiher, M. Statistical Analysis of Semiclassical Dispersion Corrections. J. Chem. Theory Comput. 2018, 14, 2480– 2494, DOI: 10.1021/acs.jctc.8b00078Google Scholar153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmvVaqsL4%253D&md5=723d9ba5398927668bdedd0141a9b508Statistical Analysis of Semiclassical Dispersion CorrectionsWeymuth, Thomas; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (5), 2480-2494CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Semiclassical dispersion corrections developed by Grimme and co-workers have become indispensable in applications of Kohn-Sham d. functional theory. A deeper understanding of the underlying parametrization might be crucial for well-founded further improvements of this successful approach. To this end, we present an in-depth assessment of the fit parameters present in semiclassical (D3-type) dispersion corrections by means of a statistically rigorous anal. We find that the choice of the cost function generally has a small effect on the empirical parameters of D3-type dispersion corrections with respect to the ref. set under consideration. Only in a few cases, the choice of cost function has a surprisingly large effect on the total dispersion energies. In particular, the weighting scheme in the cost function can significantly affect the reliability of predictions. In order to obtain unbiased (data-independent) uncertainty ests. for both the empirical fit parameters and the corresponding predictions, we carried out a nonparametric bootstrap anal. This anal. reveals that the std. deviation of the mean of the empirical D3 parameters is small. Moreover, the mean prediction uncertainty obtained by bootstrapping is not much larger than previously reported error measures. On the basis of a jackknife anal., we find that the original ref. set is slightly skewed, but our results also suggest that this feature hardly affects the prediction of dispersion energies. Furthermore, we find that the introduction of small uncertainties to the ref. data does not change the conclusions drawn in this work. However, a rigorous anal. of error accumulation arising from different parametrizations reveals that error cancellation does not necessarily occur, leading to a monotonically increasing deviation in the dispersion energy with increasing mol. size. We discuss this issue in detail at the prominent example of the C60 "buckycatcher". We find deviations between individual parametrizations of several tens of kilocalories per mol in some cases. Hence, in combination with any calcn. of dispersion energies, we recommend to always det. the assocd. uncertainties for which we will provide a software tool.
- 154Proppe, J.; Husch, T.; Simm, G. N.; Reiher, M. Uncertainty quantification for quantum chemical models of complex reaction networks. Faraday Discuss. 2016, 195, 497– 520, DOI: 10.1039/C6FD00144KGoogle Scholar154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFantbbF&md5=72ef620f8bd4517eb0c2c46fa32a05afUncertainty quantification for quantum chemical models of complex reaction networksProppe, Jonny; Husch, Tamara; Simm, Gregor N.; Reiher, MarkusFaraday Discussions (2016), 195 (Reaction Rate Theory), 497-520CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)A review. For the quant. understanding of complex chem. reaction mechanisms, it is, in general, necessary to accurately det. the corresponding free energy surface and to solve the resulting continuous-time reaction rate equations for a continuous state space. For a general (complex) reaction network, it is computationally hard to fulfill these two requirements. However, it is possible to approx. address these challenges in a phys. consistent way. On the one hand, it may be sufficient to consider approx. free energies if a reliable uncertainty measure can be provided. On the other hand, a highly resolved time evolution may not be necessary to still det. quant. fluxes in a reaction network if one is interested in specific time scales. In this paper, we present discrete-time kinetic simulations in discrete state space taking free energy uncertainties into account. The method builds upon thermo-chem. data obtained from electronic structure calcns. in a condensed-phase model. Our kinetic approach supports the anal. of general reaction networks spanning multiple time scales, which is here demonstrated for the example of the formose reaction. An important application of our approach is the detection of regions in a reaction network which require further investigation, given the uncertainties introduced by both approx. electronic structure methods and kinetic models. Such cases can then be studied in greater detail with more sophisticated first-principles calcns. and kinetic simulations.
- 155Simm, G.; Reiher, M. Error-Controlled Exploration of Chemical Reaction Networks with Gaussian Processes. J. Chem. Theory Comput. 2018, 14, 5238– 5248, DOI: 10.1021/acs.jctc.8b00504Google Scholar155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1Gmt7vK&md5=116ed9b1481210ec5564eb6e1d0157f8Error-Controlled Exploration of Chemical Reaction Networks with Gaussian ProcessesSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5238-5248CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For a theor. understanding of the reactivity of complex chem. systems, relative energies of stationary points on potential energy hypersurfaces need to be calcd. to high accuracy. Due to the large no. of intermediates present in all but the simplest chem. processes, approx. quantum chem. methods are required that allow for fast evaluations of the relative energies but at the expense of accuracy. Despite the plethora of benchmark studies, the accuracy of a quantum chem. method is often difficult to assess. Moreover, a significant improvement of a method's accuracy (e.g., through reparameterization or systematic model extension) is rarely possible. Here, we present a new approach that allows for the systematic, problem-oriented, and rolling improvement of quantum chem. results through the application of Gaussian processes. Due to its Bayesian nature, reliable error ests. are provided for each prediction. A ref. method of high accuracy can be employed if the uncertainty assocd. with a particular calcn. is above a given threshold. The new data point is then added to a growing data set in order to continuously improve the model and, as a result, all subsequent predictions. Previous predictions are validated by the updated model to ensure that uncertainties remain within the given confidence bound, which we call backtracking. We demonstrate our approach with the example of a complex chem. reaction network.
- 156Lagorce, D.; Pencheva, T.; Villoutreix, B. O.; Miteva, M. A. DG-AMMOS: A New Tool to Generate 3D Conformation of Small Molecules Using Distance Geometry and Automated Molecular Mechanics Optimization for in Silico Screening. BMC Chem. Biol. 2009, 9, 6, DOI: 10.1186/1472-6769-9-6Google Scholar156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjnsVKrtA%253D%253D&md5=6722e659d6b334955fbc5239df28e37fDG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screeningLagorce David; Villoutreix Bruno O; Miteva Maria A; Pencheva TaniaBMC chemical biology (2009), 9 (), 6 ISSN:.BACKGROUND: Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. RESULTS: Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. CONCLUSION: DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.
- 157Riniker, S.; Landrum, G. A. Better Informed Distance Geometry: Using What We Know To Improve Conformation Generation. J. Chem. Inf. Model. 2015, 55, 2562– 2574, DOI: 10.1021/acs.jcim.5b00654Google Scholar157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVeqsrjP&md5=8ee6d7d1999924fc2b42f76577f8ec51Better Informed Distance Geometry: Using What We Know To Improve Conformation GenerationRiniker, Sereina; Landrum, Gregory A.Journal of Chemical Information and Modeling (2015), 55 (12), 2562-2574CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Small org. mols. are often flexible, i.e., they can adopt a variety of low-energy conformations in soln. that exist in equil. with each other. Two main search strategies are used to generate representative conformational ensembles for mols.: systematic and stochastic. In the first approach, each rotatable bond is sampled systematically in discrete intervals, limiting its use to mols. with a small no. of rotatable bonds. Stochastic methods, however, sample the conformational space of a mol. randomly and can thus be applied to more flexible mols. Different methods employ different degrees of exptl. data for conformer generation. So-called knowledge-based methods use predefined libraries of torsional angles and ring conformations. In the distance geometry approach, however, a smaller amt. of empirical information was used, i.e., ideal bond lengths, ideal bond angles, and a few ideal torsional angles. Distance geometry is a computationally fast method to generate conformers, but it has the downside that purely distance-based constraints tend to lead to distorted arom. rings and sp2 centers. To correct this, the resulting conformations are often minimized with a force field, adding computational complexity and run time. Here the authors present an alternative strategy that combines the distance geometry approach with exptl. torsion-angle preferences obtained from small-mol. crystallog. data. The torsional angles are described by a previously developed set of hierarchically structured SMARTS patterns. The new approach is implemented in the open-source cheminformatics library RDKit, and its performance is assessed by comparing the diversity of the generated ensemble and the ability to reproduce crystal conformations taken from the crystal structures of small mols. and protein-ligand complexes.
- 158Vainio, M. J.; Johnson, M. S. Generating Conformer Ensembles Using a Multiobjective Genetic Algorithm. J. Chem. Inf. Model. 2007, 47, 2462– 2474, DOI: 10.1021/ci6005646Google Scholar158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVOnsL7L&md5=e621e6eedf3d93ff6236bc4887f25e35Generating Conformer Ensembles Using a Multiobjective Genetic AlgorithmVainio, Mikko J.; Johnson, Mark S.Journal of Chemical Information and Modeling (2007), 47 (6), 2462-2474CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The task of generating a nonredundant set of low-energy conformations for small mols. is of fundamental importance for many mol. modeling and drug-design methodologies. Several approaches to conformer generation have been published. Exhaustive searches suffer from the exponential growth of the search space with increasing degrees of conformational freedom (no. of rotatable bonds). Stochastic algorithms do not suffer as much from the exponential increase of search space and provide a good coverage of the energy min. Here, the use of a multiobjective genetic algorithm in the generation of conformer ensembles is investigated. Distance geometry is used to generate an initial conformer, which is then subject to geometric modifications encoded by the individuals of the genetic algorithm. The geometric modifications apply to torsion angles about rotatable bonds, stereochem. of double bonds and tetrahedral chiral centers, and ring conformations. The geometric diversity of the evolving conformer ensemble is preserved by a fitness-sharing mechanism based on the root-mean-square distance of the at. coordinates. Mol. symmetry is taken into account in the distance calcn. The geometric modifications introduce strain into the structures. The strain is relaxed using an MMFF94-like force field in a postprocessing step that also removes conformational duplicates and structures whose strain energy remains above a predefined window from the min. energy value found in the set. The implementation, called Balloon, is available free of charge on the Internet (http://www.abo.fi/∼mivainio/balloon/).
- 159Leite, T. B.; Gomes, D.; Miteva, M. A.; Chomilier, J.; Villoutreix, B. O.; Tufféry, P. Frog: A FRee Online druG 3D Conformation Generator. Nucleic Acids Res. 2007, 35, W568– W572, DOI: 10.1093/nar/gkm289Google ScholarThere is no corresponding record for this reference.
- 160Miteva, M. A.; Guyon, F.; Tufféry, P. Frog2: Efficient 3D Conformation Ensemble Generator for Small Compounds. Nucleic Acids Res. 2010, 38, W622– W627, DOI: 10.1093/nar/gkq325Google Scholar160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXotVSqsr8%253D&md5=ec1c9860de9eb1e81e9e8d81f24f550bFrog2: Efficient 3D conformation ensemble generator for small compoundsMiteva, Maria A.; Guyon, Frederic; Tuffery, PierreNucleic Acids Research (2010), 38 (Web Server), W622-W627CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)Frog is a web tool dedicated to small compd. 3D generation. Here we present the new version, Frog2, which allows the generation of conformation ensembles of small mols. starting from either 1D, 2D or 3D description of the compds. From a compd. description in one of the SMILES, SDF or mol2 formats, the server will return an ensemble of diverse conformers generated using a two stage Monte Carlo approach in the dihedral space. When starting from 1D or 2D description of compds., Frog2 is capable to detect the sites of ambiguous stereoisomery, and thus to sample different stereoisomers. Frog2 also embeds new energy minimization and ring generation facilities that solve the problem of some missing cycle structures in the Frog1 ring library. Finally, the optimized generator of conformation ensembles in Frog2 results in a gain of computational time permitting Frog2 to be up to 20 times faster that Frog1, while producing satisfactory conformations in terms of structural quality and conformational diversity. The high speed and the good quality of generated conformational ensembles makes it possible the treatment of larger compd. collections using Frog2. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/Frog2.
- 161Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model. 2010, 50, 572– 584, DOI: 10.1021/ci100031xGoogle Scholar161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjtlaisrY%253D&md5=fb87ecc9c51eddef63b41fffcd9babeeConformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural DatabaseHawkins, Paul C. D.; Skillman, A. Geoffrey; Warren, Gregory L.; Ellingson, Benjamin A.; Stahl, Matthew T.Journal of Chemical Information and Modeling (2010), 50 (4), 572-584CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Here, we present the algorithm and validation for OMEGA, a systematic, knowledge-based conformer generator. The algorithm consists of three phases: assembly of an initial 3D structure from a library of fragments; exhaustive enumeration of all rotatable torsions using values drawn from a knowledge-based list of angles, thereby generating a large set of conformations; and sampling of this set by geometric and energy criteria. Validation of conformer generators like OMEGA has often been undertaken by comparing computed conformer sets to exptl. mol. conformations from crystallog., usually from the Protein Databank (PDB). Such an approach is fraught with difficulty due to the systematic problems with small mol. structures in the PDB. Methods are presented to identify a diverse set of small mol. structures from cocomplexes in the PDB that has maximal reliability. A challenging set of 197 high quality, carefully selected ligand structures from well-solved models was obtained using these methods. This set will provide a sound basis for comparison and validation of conformer generators in the future. Validation results from this set are compared to the results using structures of a set of druglike mols. extd. from the Cambridge Structural Database (CSD). OMEGA is found to perform very well in reproducing the crystallog. conformations from both these data sets using two complementary metrics of success.
- 162Schärfer, C.; Schulz-Gasch, T.; Hert, J.; Heinzerling, L.; Schulz, B.; Inhester, T.; Stahl, M.; Rarey, M. CONFECT: Conformations from an Expert Collection of Torsion Patterns. ChemMedChem 2013, 8, 1690– 1700, DOI: 10.1002/cmdc.201300242Google Scholar162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sfotVymtA%253D%253D&md5=9aed22ca5ec1872aea505dadb9d99baeCONFECT: conformations from an expert collection of torsion patternsScharfer Christin; Schulz-Gasch Tanja; Hert Jerome; Heinzerling Lennart; Schulz Benjamin; Inhester Therese; Stahl Martin; Rarey MatthiasChemMedChem (2013), 8 (10), 1690-700 ISSN:.The generation of sets of low-energy conformations for a given molecule is a central task in drug design. Herein we present a new conformation generator called CONFECT that builds on our previously published library of torsion patterns. Conformations are generated as well as ranked by means of normalized frequency distributions derived from the Cambridge Structural Database (CSD). Following an incremental construction approach, conformations are selected from a systematic enumeration within energetic boundaries. The new tool is benchmarked in several different ways, indicating that it allows the efficient generation of high-quality conformation ensembles. These ensembles are smaller than those produced by state-of-the-art tools, yet they effectively cover conformational space.
- 163Guba, W.; Meyder, A.; Rarey, M.; Hert, J. Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules. J. Chem. Inf. Model. 2016, 56, 1– 5, DOI: 10.1021/acs.jcim.5b00522Google Scholar163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XovFKjsA%253D%253D&md5=0e26d363bad3069851a04bf977027f53Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small MoleculesGuba, Wolfgang; Meyder, Agnes; Rarey, Matthias; Hert, JeromeJournal of Chemical Information and Modeling (2016), 56 (1), 1-5CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The Torsion Library contains hundreds of rules for small mol. conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by mol. design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have systematically revised all torsion rules to better identify highly strained conformations and minimize the no. of false alerts for CSD small mol. X-ray structures. For this new release, we added or substantially modified 78 torsion patterns and reviewed all angles and tolerance intervals. The overall no. of red alerts for a filtered CSD data set with 130 000 structures was reduced by a factor of 4 compared to the predecessor. This is of clear advantage in 3D virtual screening where hits should only be removed by a conformational filter if they are in energetically inaccessible conformations.
- 164Batter, J.; Brooks, F. GROPE-I: A Computer Display to the Sense of Feel. Proceedings of the International Federation of Information Processing 1971, 759– 763Google ScholarThere is no corresponding record for this reference.
- 165Noll, A. M. Man-Machine Tactile Communication. J. Soc. Inform. Dis. 1972, 6–11, 30Google ScholarThere is no corresponding record for this reference.
- 166Atkinson, W. D.; Bond, K. E.; Tribble, G. L.; Wilson, K. R. Computing with Feeling. Comp. and Graph. 1977, 2, 97– 103, DOI: 10.1016/0097-8493(77)90009-7Google ScholarThere is no corresponding record for this reference.
- 167Lancaster, S. J. Immersed in virtual molecules. Nature Rev. Chem. 2018, 2, 253– 254, DOI: 10.1038/s41570-018-0043-5Google Scholar167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVKnsb3M&md5=886aaa061e23d04e29d0b2bdc99df026Immersed in virtual moleculesLancaster, Simon J.Nature Reviews Chemistry (2018), 2 (10), 253-254CODEN: NRCAF7; ISSN:2397-3358. (Nature Research)A full grasp of chem. requires students to be able to connect microscopic reality with symbolic representations. Immersive virtual reality provides a soln. for those who need a tangible link between these representations.
- 168Aspuru-Guzik, A.; Lindh, R.; Reiher, M. The Matter (R)evolution. ACS Cent. Sci. 2018, 4, 144– 152, DOI: 10.1021/acscentsci.7b00550Google Scholar168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitF2gsrk%253D&md5=b606a11b4272d62ae4f7de4b7709d25aThe Matter Simulation (R)evolutionAspuru-Guzik, Alan; Lindh, Roland; Reiher, MarkusACS Central Science (2018), 4 (2), 144-152CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)To date, the program for the development of methods and models for atomistic and continuum simulation directed toward chems. and materials has reached an incredible degree of sophistication and maturity. Currently, one can witness an increasingly rapid emergence of advances in computing, artificial intelligence, and robotics. This drives us to consider the future of computer simulation of matter from the mol. to the human length and time scales in a radical way that deliberately dares to go beyond the foreseeable next steps in any given discipline. This perspective article presents a view on this future development that we believe is likely to become a reality during our lifetime.
- 169Matthews, D. Science goes virtual. Nature 2018, 557, 127– 128, DOI: 10.1038/d41586-018-04997-2Google ScholarThere is no corresponding record for this reference.
- 170Cruz-Neira, C.; Sandin, D. J.; DeFanti, T. A. Surround-Screen Projection-Based Virtual Reality: The Design and Implementation of the CAVE. Proceedings of the 20th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, NY, USA, 1993; pp 135– 142.Google ScholarThere is no corresponding record for this reference.
- 171Ai, Z.; Fröhlich, T. Molecular Dynamics Simulation in Virtual Environments. Comput. Graphics Forum 1998, 17, 267– 273, DOI: 10.1111/1467-8659.00273Google ScholarThere is no corresponding record for this reference.
- 172Prins, J. F.; Hermans, J.; Mann, G.; Nyland, L. S.; Simons, M. A Virtual Environment for Steered Molecular Dynamics. Future Gener. Comp. Sy. 1999, 15, 485– 495, DOI: 10.1016/S0167-739X(99)00005-9Google ScholarThere is no corresponding record for this reference.
- 173Ǩrenek, A. Haptic Rendering of Complex Force Fields. Proceedings of the Workshop on Virtual Environments 2003; ACM: New York, NY, USA, 2003; pp 231– 239.Google ScholarThere is no corresponding record for this reference.
- 174Lee, Y.-G.; Lyons, K. W. Smoothing Haptic Interaction Using Molecular Force Calculations. Comput.-Aided Design 2004, 36, 75– 90, DOI: 10.1016/S0010-4485(03)00080-0Google ScholarThere is no corresponding record for this reference.
- 175Morin, S.; Redon, S. A Force-Feedback Algorithm for Adaptive Articulated-Body Dynamics Simulation. IEEE International Conference on Robotics and Automation; IEEE, 2007; pp 3245– 3250.Google ScholarThere is no corresponding record for this reference.
- 176Daunay, B.; Régnier, S. Stable Six Degrees of Freedom Haptic Feedback for Flexible Ligand-Protein Docking. Comput.-Aided Design 2009, 41, 886– 895, DOI: 10.1016/j.cad.2009.06.010Google ScholarThere is no corresponding record for this reference.
- 177Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Haptic Feedback for Molecular Simulation. 2009 IEEE/RSJ. International Conference on Intelligent Robots and Systems; IEEE, 2009; pp 237– 242.Google ScholarThere is no corresponding record for this reference.
- 178Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Comparing Position and Force Control for Interactive Molecular Simulators with Haptic Feedback. J. Mol. Graphics Modell. 2010, 29, 280– 289, DOI: 10.1016/j.jmgm.2010.06.003Google Scholar178https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFamtLvP&md5=8d81e29d4693725c0ada3ce7db0cebc0Comparing position and force control for interactive molecular simulators with haptic feedbackBolopion, Aude; Cagneau, Barthelemy; Redon, Stephane; Regnier, StephaneJournal of Molecular Graphics & Modelling (2010), 29 (2), 280-289CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)This paper presents a novel tool for the anal. of new mol. structures which enables a wide variety of manipulations. It is composed of a mol. simulator and a haptic device. The simulation software deals with systems of hundreds or thousands of degrees of freedom and computes the reconfiguration of the mols. in a few tenths of a second. For the ease of manipulation and to help the operator understand nanoscale phenomena, a haptic device is connected to the simulator. To handle a wide variety of applications, both position and force control are implemented. To our knowledge, this is the first time the applications of force control are detailed for mol. simulation. These two control modes are compared in terms of adequacy with mol. dynamics, transparency and stability sensitivity with respect to environmental conditions. Based on their specificity the operations they can realize are detailed. Expts. highlight the usability of our tool for the different steps of the anal. of mol. structures. It includes the global reconfiguration of a mol. system, the measurement of mol. properties and the comprehension of nanoscale interactions. Compared to most existing systems, the one developed in this paper offers a wide range of possible expts. The detailed anal. of the properties of the control modes can be easily used to implement haptic feedback on other mol. simulators.
- 179Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Haptic Molecular Simulation Based on Force Control. 2010 IEEE/ASME International Conference on Advanced Intelligent Mechatronics; IEEE, 2010; pp 329– 334.Google ScholarThere is no corresponding record for this reference.
- 180Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Variable Gain Haptic Coupling for Molecular Simulation. 2011 IEEE World Haptics Conference; IEEE, 2011; pp 469– 474.Google ScholarThere is no corresponding record for this reference.
- 181Durlach, N.; Mavor, A.; Development, C.; Board, C.; Council, N. Virtual Reality: Scientific and Technological Challenges; National Academies Press, 1994.Google ScholarThere is no corresponding record for this reference.
- 182Mark, W. R.; Randolph, S. C.; Finch, M.; Van Verth, J. M.; Taylor, R. M., II. Adding Force Feedback to Graphics Systems: Issues and Solutions. Proceedings of the 23rd Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1996; pp 447– 452.Google ScholarThere is no corresponding record for this reference.
- 183Ruspini, D. C.; Kolarov, K.; Khatib, O. The Haptic Display of Complex Graphical Environments. Proceedings of the 24th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1997; pp 345– 352.Google ScholarThere is no corresponding record for this reference.
- 184Cruz-Neira, C.; Langley, R.; Bash, P. VIBE: A Virtual Biomolecular Environment for Interactive Molecular Modeling. Comput. Chem. 1996, 20, 469– 477, DOI: 10.1016/0097-8485(96)00009-5Google Scholar184https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XlslWhu7Y%253D&md5=c1c2ca7665c30f7500d6b2e721dc29e0VIBE: a virtual biomolecular environment for interactive molecular modelingCruz-Neira, C.; Langley, R.; Bash, P. A.Computers & Chemistry (Oxford) (1996), 20 (4), 469-477CODEN: COCHDK; ISSN:0097-8485. (Elsevier)Virtual reality tightly coupled to high performance computing and communications ushers in a new era for the study of mol. recognition and the rational design of pharmaceutical compds. We have created a Virtual Biomol. Environment (VIBE), which consists of (1) massively parallel computing to simulate the phys. and chem. properties of a mol. system, (2) the Cave Automatic Virtual Environment (CAVE) for immersive display and interaction with the mol. system, and (3) a high-speed network interface to exchange data between the simulation and the CAVE. VIBE enables mol. scientists to have a visual, auditory, and haptic experience with a chem. system, while simultaneously manipulating its phys. properties by steering, in real-time, a simulation executed on a supercomputer. We demonstrate the characteristics of VIBE using a HIV protease-cyclic urea inhibitor complex.
- 185Férey, N.; Nelson, J.; Martin, C.; Picinali, L.; Bouyer, G.; Tek, A.; Bourdot, P.; Burkhardt, J.; Katz, B.; Ammi, M.; Etchebest, C.; Autin, L. Multisensory VR Interaction for Protein-Docking in the CoRSAIRe Project. Virtual Reality 2009, 13, 273– 293, DOI: 10.1007/s10055-009-0136-zGoogle ScholarThere is no corresponding record for this reference.
- 186Glowacki, D. R.; O’Connor, M.; Calabro, G.; Price, J.; Tew, P.; Mitchell, T.; Hyde, J.; Tew, D. P.; Coughtrie, D. J.; McIntosh-Smith, S. A GPU-Accelerated Immersive Audio-Visual Framework for Interaction with Molecular Dynamics Using Consumer Depth Sensors. Faraday Discuss. 2014, 169, 63– 87, DOI: 10.1039/C4FD00008KGoogle ScholarThere is no corresponding record for this reference.
- 187Arbon, R. E.; Jones, A. J.; Bratholm, L. A.; Mitchell, T.; Glowacki, D. R. Sonifying Stochastic Walks on Biomolecular Energy Landscapes. 2018, arXiv 1803.05805.Google ScholarThere is no corresponding record for this reference.
- 188Ouh-young, M.; Pique, M.; Hughes, J.; Srinivasan, N.; Brooks, F. P. Using a Manipulator for Force Display in Molecular Docking. IEEE International Conference on Robotics and Automation; IEEE, 1988; pp 1824– 1829.Google ScholarThere is no corresponding record for this reference.
- 189Brooks, F. P., Jr.; Ouh-Young, M.; Batter, J. J.; Jerome Kilpatrick, P. Project GROPE — Haptic Displays for Scientific Visualization. SIGGRAPH Comput. Graph. 1990, 24, 177– 185, DOI: 10.1145/97880.97899Google ScholarThere is no corresponding record for this reference.
- 190Levine, D.; Facello, M.; Hallstrom, P.; Reeder, G.; Walenz, B.; Stevens, F. Stalk: An Interactive System for Virtual Molecular Docking. IEEE Comput. Sci. Eng. 1997, 4, 55– 65, DOI: 10.1109/99.609834Google Scholar190https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkslOksro%253D&md5=13346f7b2c9a5751e55e859fea6dc97dStalk: an interactive system for virtual molecular dockingLevine, David; Facello, Michael; Hallstrom, Philip; Reeder, Gregory; Walenz, Brian; Stevens, FredIEEE Computational Science & Engineering (1997), 4 (2), 55-65CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)Several recent technols., i.e., genetic algorithms, parallel and distributed computing, virtual reality, and high-speed networking, underlie a new approach to the computational study of how biomols. interact or dock together. With the Stalk system, a user in a virtual reality environment can interact with a genetic algorithm running on a parallel computer to help in the search for likely geometric configurations.
- 191Brooks, F. P., Jr. Impressions by a dinosaur. Faraday Discuss. 2014, 169, 521– 527, DOI: 10.1039/C4FD00130CGoogle ScholarThere is no corresponding record for this reference.
- 192O’Connor, M.; Deeks, H. M.; Dawn, E.; Metatla, O.; Roudaut, A.; Sutton, M.; Thomas, L. M.; Glowacki, B. R.; Sage, R.; Tew, P.; Wonnacott, M.; Bates, P.; Mulholland, A. J.; Glowacki, D. R. Sampling Molecular Conformations and Dynamics in a Multiuser Virtual Reality Framework. Sci. Adv. 2018, 4, eaat2731 DOI: 10.1126/sciadv.aat2731Google ScholarThere is no corresponding record for this reference.
- 193Bayazit, O.; Song, G.; Amato, N. Ligand Binding with OBPRM and User Input. IEEE International Conference on Robotics and Automation; IEEE, 2001; pp 954– 959.Google ScholarThere is no corresponding record for this reference.
- 194Nagata, H.; Mizushima, H.; Tanaka, H. Concept and Prototype of Protein-Ligand Docking Simulator with Force Feedback Technology. Bioinformatics 2002, 18, 140– 146, DOI: 10.1093/bioinformatics/18.1.140Google ScholarThere is no corresponding record for this reference.
- 195Lai-Yuen, S. K.; Lee, Y.-S. Computer-Aided Molecular Design (CAMD) with Force-Torque Feedback. Ninth International Conference on Computer Aided Design and Computer Graphics; ACM: New York, 2005; pp 199– 204.Google ScholarThere is no corresponding record for this reference.
- 196Birmanns, S.; Wriggers, W. Interactive Fitting Augmented by Force-Feedback and Virtual Reality. J. Struct. Biol. 2003, 144, 123– 131, DOI: 10.1016/j.jsb.2003.09.018Google ScholarThere is no corresponding record for this reference.
- 197Wollacott, A. M.; Merz, K. M., Jr. Haptic Applications for Molecular Structure Manipulation. J. Mol. Graphics Modell. 2007, 25, 801– 805, DOI: 10.1016/j.jmgm.2006.07.005Google Scholar197https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsFOiu7w%253D&md5=53a6dc20d08d1a0de0cee9053589ddf9Haptic applications for molecular structure manipulationWollacott, Andrew M.; Merz, Kenneth M.Journal of Molecular Graphics & Modelling (2007), 25 (6), 801-805CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Inc.)We describe the application of haptic technol. to enhance the information available in chem. systems, specifically related to computational drug design. These methods are designed to build upon the visual information presented by mol. viewers and add the sensation of touch, or force feedback. The addn. of sensory input can aid in the anal. of mol. structures and the understanding of intermol. interactions by delivering chem. relevant forces to the end user.
- 198Subasi, E.; Basdogan, C. A New Haptic Interaction and Visualization Approach for Rigid Molecular Docking in Virtual Environments. Presence 2008, 17, 73– 90, DOI: 10.1162/pres.17.1.73Google ScholarThere is no corresponding record for this reference.
- 199Heyd, J.; Birmanns, S. Immersive Structural Biology: A New Approach to Hybrid Modeling of Macromolecular Assemblies. Virtual Reality 2009, 13, 245– 255, DOI: 10.1007/s10055-009-0129-yGoogle ScholarThere is no corresponding record for this reference.
- 200Anthopoulos, A.; Pasqualetto, G.; Grimstead, I.; Brancale, A. Haptic-Driven, Interactive Drug Design: Implementing a GPU-Based Approach to Evaluate the Induced Fit Effect. Faraday Discuss. 2014, 169, 323– 342, DOI: 10.1039/C3FD00139CGoogle Scholar200https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jE&md5=baa69798111ce24fac6a771e906d262eHaptic-driven, interactive drug design: implementing a GPU-based approach to evaluate the induced fit effectAnthopoulos, Athanasios; Pasqualetto, Gaia; Grimstead, Ian; Brancale, AndreaFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 323-342CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)In this paper, we describe a hybrid meta-heuristics method of energy minimization and conformational sampling and its application into our haptic-driven mol. modeling simulator. The proposed method has been designed to suit real-time mol. docking simulations, where the time-lapse between two successive ligand poses is relatively small. In these situations, the energy minimization problem becomes increasingly complex and chaotic. The algorithm is tuned to take advantage of recent advances in GPU computing with asynchronous kernel execution, which has allowed us to include full protein flexibility in the real-time interactive, haptic-driven simulations. Finally, in this paper, we will also discuss the implementation of such high-performance computing approaches in our software, discussing the results of our initial validation studies, highlighting the advantages and limitations of such interactive methodol.
- 201Iakovou, G.; Hayward, S.; Laycock, S. D. A Real-Time Proximity Querying Algorithm for Haptic-Based Molecular Docking. Faraday Discuss. 2014, 169, 359– 377, DOI: 10.1039/C3FD00123GGoogle Scholar201https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jP&md5=ba322c73d491c8d3218f2ec2e97f4a3fA real-time proximity querying algorithm for haptic-based molecular dockingIakovou, Georgios; Hayward, Steven; Laycock, StephenFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 359-377CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Intermol. binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacol. properties of drugs. Mol. docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the mols. to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calcn. of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calcns. must be performed within 1ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (esp. for large mols.), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermol. forces in real time. Our motivation is the eventual development of a haptic-based docking soln. that can model mol. flexibility. Uniquely in a haptics application we use octrees to decomp. the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calcns. are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large mol. structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, mol. docking application called Haptimol_RD. The user can use the haptic device to orientate the mols. in space, sense the interaction forces on the device, and guide the mols. to their binding pose. Haptimol_RD is designed to run on consumer level hardware, i.e. there is no need for specialized/proprietary hardware.
- 202Iakovou, G.; Hayward, S.; Laycock, S. D. Adaptive GPU-Accelerated Force Calculation for Interactive Rigid Molecular Docking Using Haptics. J. Mol. Graphics Modell. 2015, 61, 1– 12, DOI: 10.1016/j.jmgm.2015.06.003Google Scholar202https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2ksbzL&md5=fc7fcb1082a8e50b08323d4ab720b249Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using hapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Molecular Graphics & Modelling (2015), 61 (), 1-12CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)Mol. docking systems model and simulate in silico the interactions of intermol. binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch, but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500 Hz to 1 kHz. The authors present an adaptive force calcn. approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to mol. simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to det. the set of interat. interactions within a cutoff distance. The total force is then calcd. from this set. The approach can achieve force updates in <2 ms for mol. structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calcn. approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates.
- 203Iakovou, G.; Hayward, S.; Laycock, S. D. Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics. J. Chem. Inf. Model. 2017, 57, 1142– 1152, DOI: 10.1021/acs.jcim.7b00051Google Scholar203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmsVahs74%253D&md5=88a043fa234a92e12c81dfd453884b01Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with HapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Chemical Information and Modeling (2017), 57 (5), 1142-1152CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Haptic technol. facilitates user interaction with the virtual world via the sense of touch. In mol. docking, haptics enables the user to sense the interaction forces during the docking process. Here the authors describe a haptics-assisted interactive software tool, called Haptimol_RD, for the study of docking interactions. By utilizing GPU-accelerated proximity querying methods very large systems can now be studied. Methods for force scaling, multipoint collision response and haptic navigation are described that address force stability issues that are particular to the interactive docking of large systems. Thus, Haptimol_RD expands, for the first time, the use of interactive biomol. haptics to the study of protein-protein interactions. Unlike existing approaches, Haptimol_RD is designed to run on relatively inexpensive consumer-level hardware and is freely available to the community.
- 204Izrailev, S.; Stepaniants, S.; Isralewitz, B.; Kosztin, D.; Lu, H.; Molnar, F.; Wriggers, W.; Schulten, K. In Computational Molecular Dynamics: Challenges, Methods, Ideas; Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A., Reich, S., Skeel, R., Eds.; Lecture Notes in Computational Science and Engineering; Springer: Berlin, Heidelberg, 1999; Vol. 4, pp 39– 65.Google ScholarThere is no corresponding record for this reference.
- 205Grubmüller, H.; Heymann, B.; Tavan, P. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force. Science 1996, 271, 997– 999, DOI: 10.1126/science.271.5251.997Google Scholar205https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XhtFCru7g%253D&md5=8a013b443101d48aed80fcde1ec7d924Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture forceGrubmueller, Helmut; Heymann, Berthold; Tavan, PaulScience (Washington, D. C.) (1996), 271 (5251), 997-9CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The force required to rupture the streptavidin-biotin complex was calcd. here by computer simulations. The computed force agrees well with that obtained by recent single mol. at. force microscope expts. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, addnl. water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were obsd.
- 206Izrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K. Molecular Dynamics Study of Unbinding of the Avidin-Biotin Complex. Biophys. J. 1997, 72, 1568– 1581, DOI: 10.1016/S0006-3495(97)78804-0Google Scholar206https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitFeisbk%253D&md5=649ad913ebac2d1b320aebef229a8c50Molecular dynamics study of unbinding of the avidin-biotin complexIzrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K.Biophysical Journal (1997), 72 (4), 1568-1581CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)We report mol. dynamics simulations that induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force consts. close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force const. The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calcd. rupture forces exceed by far those obsd. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the assocd. Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM expts., and that simulated unbinding cannot be readily extrapolated to the exptl. obsd. rupture.
- 207Balsera, M.; Stepaniants, S.; Izrailev, S.; Oono, Y.; Schulten, K. Reconstructing Potential Energy Functions from Simulated Force-Induced Unbinding Processes. Biophys. J. 1997, 73, 1281– 1287, DOI: 10.1016/S0006-3495(97)78161-XGoogle ScholarThere is no corresponding record for this reference.
- 208Isralewitz, B.; Izrailev, S.; Schulten, K. Binding Pathway of Retinal to Bacterio-Opsin: A Prediction by Molecular Dynamics Simulations. Biophys. J. 1997, 73, 2972– 2979, DOI: 10.1016/S0006-3495(97)78326-7Google Scholar208https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnsl2murc%253D&md5=ad6760df6b7abc856b68c31980e1da86Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulationsIsralewitz, Barry; Izrailev, Sergei; Schulten, KlausBiophysical Journal (1997), 73 (6), 2972-2979CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)Formation of bacteriorhodopsin (bR) from apoprotein and retinal has been studied exptl., but the actual pathway, including the point of entry, is little understood. Mol. dynamics simulations provide a surprisingly clear prediction. A window between bR helixes E and F in the transmembrane part of the protein can be identified as an entry point for retinal. Steered mol. dynamics, performed by applying a series of external forces in the range of 200-1000 pN over a period of 0.2 ns to retinal, allows one to ext. this chromophore from bR once the Schiff base bond to Lys216 is cleaved. Extn. proceeds until the retinal tail forms a hydrogen bond network with the Ala144, Met145, and Ser183 side groups lining the exit/entry window. The manipulation induces a distortion with a fitted root mean square deviation of coordinates (ignoring retinal, water, and hydrogen atoms) of less than 1.9 Å by the time the retinal carbonyl reaches the protein surface. The forces needed to ext. retinal are due to friction and do not indicate significant potential barriers. The simulations therefore suggest a pathway for the binding of retinal. Water mols. are found to play a crucial role in the binding process.
- 209Jarzynski, C. Nonequilibrium Equality for Free Energy Differences. Phys. Rev. Lett. 1997, 78, 2690, DOI: 10.1103/PhysRevLett.78.2690Google Scholar209https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXisVSrt7c%253D&md5=5e572f64b7e9044fff5af96867602877Nonequilibrium equality for free energy differencesJarzynski, C.Physical Review Letters (1997), 78 (14), 2690-2693CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)An expression is derived for the equil. free energy difference between two configurations of a system, in terms of an ensemble of finite-time measurements of the work performed in parametrically switching from one configuration to the other. Two well-known identities emerge as limiting cases of this result.
- 210Nelson, M.; Humphrey, W.; Kufrin, R.; Gursoy, A.; Dalke, A.; Kale, L.; Skeel, R.; Schulten, K. MDScope — a Visual Computing Environment for Structural Biology. Comput. Phys. Commun. 1995, 91, 111– 133, DOI: 10.1016/0010-4655(95)00045-HGoogle Scholar210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1Wrtrg%253D&md5=5581371fd83f3a501280347abd691318MDScope - a visual computing environment for structural biologyNelson, Mark; Humphrey, William; Kufrin, Richard; Gursoy, Attila; Dalke, Andrew; Kale, Laxmikant; Skeel, Robert; Schulten, KlausComputer Physics Communications (1995), 91 (1-3), 111-33CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier)MDScope is an integrated set of computational tools which function as an interactive visual computing environment for the simulation and study of biopolymers. This environment consists of three parts: (1) vmd, a mol. visualization program for interactive display of mol. systems; (2) namd, a mol. dynamics program designed for performance, scalability, modularity, and portability, which runs in parallel on a variety of computer platforms; (3) MDComm, a protocol and library which functions as the unifying communication agent between the visualization and simulation components of MDScope. Namd is expressly designed for distributed memory parallel architectures and uses a spatial decompn. parallelization strategy coupled with a multi-threaded, message-driven computation model which reduces inefficiencies due to communication latency. Through the MDComm software, vmd acts as a graphical interface and interactive control for namd, allowing a user running namd to utilize a parallel platform for computational power while visualizing the trajectory as it is computed. Modularity in both vmd and namd is accomplished through an object-oriented design, which facilitates the addn. of features and new algorithms.
- 211Rapaport, D. Interactive Molecular Dynamics. Phys. A 1997, 240, 246– 254, DOI: 10.1016/S0378-4371(97)00148-9Google Scholar211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkt1agtLo%253D&md5=8376a0d92a34d61102b994d2dea8e323Interactive molecular dynamicsRapaport, D. C.Physica A: Statistical and Theoretical Physics (Amsterdam) (1997), 240 (1-2), 246-254CODEN: PHYADX; ISSN:0378-4371. (Elsevier)We address the use of visualization and interactivity in mol. dynamics simulation. In an interactive environment the simulator is not only provided with the means to view the system in alternative ways in real-time, but is also able to 'steer' the computation in different directions by changing the governing parameters of the system. The simulational experience can be enhanced significantly by such means. Several examples are outlined.
- 212Rapaport, D. C. An Introduction to Interactive Molecular-Dynamics Simulations. Comput. Phys. 1997, 11, 337– 347, DOI: 10.1063/1.168612Google Scholar212https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmsVCiurs%253D&md5=dd6d05d9bec0be44a4f0deb1ea2828b8An introduction to interactive molecular-dynamics simulationsRapaport, D. C.Computers in Physics (1997), 11 (4), 337-347CODEN: CPHYE2; ISSN:0894-1866. (American Institute of Physics)A review with 8 refs.
- 213Leech, J.; Prins, J. F.; Hermans, J. SMD: Visual Steering of Molecular Dynamics for Protein Design. IEEE Comput. Sci. Eng. 1996, 3, 38– 45, DOI: 10.1109/99.556511Google Scholar213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitlSqtQ%253D%253D&md5=6f7100b4048a22f1cdc0a43ab30048b4SMD: visual steering of molecular dynamics for protein designLeech, Jonathan; Prins, Jan F.; Hermans, JanIEEE Computational Science & Engineering (1996), 3 (4), 38-45CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)SMD, a system for interactively steering mol. dynamics calcns. of protein mols., includes computation, visualization, and communications components. Biochemists can "tug" mols. into different shapes by specifying external forces in the graphical interface, which are added to internal forces representing at. bonds and nonbonded interactions.
- 214Vormoor, O. Quick and Easy Interactive Molecular Dynamics Using Java3D. Comput. Sci. Eng. 2001, 3, 98– 104, DOI: 10.1109/5992.947113Google Scholar214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFOjt7w%253D&md5=a5b57a2dc0a27f019479fdedba6a44a8Quick and easy interactive molecular dynamics using Java3DVormoor, OliverComputing in Science & Engineering (2001), 3 (5), 98-104CODEN: CSENFA; ISSN:1521-9615. (American Institute of Physics)An interactive mol. dynamics software, called Java Interactive Mol. Dynamics (JIMD), was developed for the study of colloid clusters. JIMD is not a stand-alone interactive mol. dynamic application, but a software package that can be quickly and easily adapted to existing mol. dynamics simulation software. For rendering the mol. system, JIMD uses Java3D, the application programing interface for writing 3D graphics applications in Java.
- 215Stone, J. E.; Gullingsrud, J.; Schulten, K. A System for Interactive Molecular Dynamics Simulation. Proceedings of the 2001 Symposium on Interactive 3D Graphics; ACM: New York, NY, USA, 2001; pp 191– 194.Google ScholarThere is no corresponding record for this reference.
- 216Grayson, P.; Tajkhorshid, E.; Schulten, K. Mechanisms of Selectivity in Channels and Enzymes Studied with Interactive Molecular Dynamics. Biophys. J. 2003, 85, 36– 48, DOI: 10.1016/S0006-3495(03)74452-XGoogle ScholarThere is no corresponding record for this reference.
- 217Férey, N.; Delalande, O.; Grasseau, G.; Baaden, M. A VR Framework for Interacting with Molecular Simulations. Proceedings of the 2008 ACM Symposium on Virtual Reality Software and Technology; ACM: New York, NY, USA, 2008; pp 91– 94.Google ScholarThere is no corresponding record for this reference.
- 218Dreher, M.; Piuzzi, M.; Turki, A.; Chavent, M.; Baaden, M.; Férey, N.; Limet, S.; Raffin, B.; Robert, S. Interactive Molecular Dynamics: Scaling up to Large Systems. Procedia Comput. Sci. 2013, 18, 20– 29, DOI: 10.1016/j.procs.2013.05.165Google ScholarThere is no corresponding record for this reference.
- 219Dreher, M.; Prevoteau-Jonquet, J.; Trellet, M.; Piuzzi, M.; Baaden, M.; Raffin, B.; Ferey, N.; Robert, S.; Limet, S. ExaViz: A Flexible Framework to Analyse, Steer and Interact with Molecular Dynamics Simulations. Faraday Discuss. 2014, 169, 119– 142, DOI: 10.1039/C3FD00142CGoogle ScholarThere is no corresponding record for this reference.
- 220Stone, J. E.; Kohlmeyer, A.; Vandivort, K. L.; Schulten, K. In Advances in Visual Computing; Bebis, G., Boyle, R., Parvin, B., Koracin, D., Chung, R., Hammound, R., Hussain, M., Kar-Han, T., Crawfis, R., Thalmann, D., Kao, D., Avila, L., Eds.; Lecture Notes in Computer Science; Springer: Berlin, Heidelberg, 2010; Vol. 6454, pp 382– 393.Google ScholarThere is no corresponding record for this reference.
- 221Luehr, N.; Jin, A. G. B.; Martínez, T. J. Ab Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs). J. Chem. Theory Comput. 2015, 11, 4536– 4544, DOI: 10.1021/acs.jctc.5b00419Google Scholar221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVeqtrzP&md5=9d5ff51b17633add948dbacc2c22958fAb Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs)Luehr, Nathan; Jin, Alex G. B.; Martinez, Todd J.Journal of Chemical Theory and Computation (2015), 11 (10), 4536-4544CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)A virtual mol. modeling kit is developed based on GPU-enabled interactive ab initio mol. dynamics (MD). The code uses the TeraChem and VMD programs with a modified IMD interface. Optimization of the GPU accelerated TeraChem program specifically for small mol. systems is discussed, and a robust multiple time step integrator is employed to accurately integrate strong user-supplied pulling forces. Smooth and responsive visualization techniques are developed to allow interactive manipulation at min. simulation rates below five MD steps per s. Representative calcns. at the Hartree-Fock level of theory are demonstrated for mol. systems contg. up to a few dozen atoms.
- 222Surles, M. C.; Richardson, J. S.; Richardson, D. C.; Brooks, F. P. Sculpting Proteins Interactively: Continual Energy Minimization Embedded in a Graphical Modeling System. Protein Sci. 1994, 3, 198– 210, DOI: 10.1002/pro.5560030205Google Scholar222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXktlSgt74%253D&md5=2138dd23c7212467e7fe17ab717eaa44Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling systemSurles, Mark C.; Richardson, Jane S.; Richardson, David C.; Brooks, Frederick P., Jr.Protein Science (1994), 3 (), 198-210CODEN: PRCIEI; ISSN:0961-8368.The authors describe a new paradigm for modeling proteins in interactive computer graphics systems - continual maintenance of a phys. valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance an all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond strengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specific springs. The graphical interface can show bad and(or) favorable contacts, and individual energy terms can be turned on or off to det. their effects and interactions. Sculpt finds a local min. of the total energy that satisfies all the constraints using an augmented Lagrange-multiplier method; calcn. time increases only linearly with the no. of atoms because the matrix of constraint gradients is sparse and banded. On a 100-MHz MIPs R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per s on a 20-residue fragment and 2 updates per s on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2-stranded β-ribbon into an approx. β-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and phys. realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and (2) they help the user understand how different energy terms interact to stabilize a given conformation. The Sculpt paradigm combines many of the best features of interactive graphical modeling, energy minimization, and actual phys. models, and the authors propose it as an esp. productive way to use current and future increases in computer speed.
- 223Hanwell, M. D.; Curtis, D. E.; Lonie, D. C.; Vandermeersch, T.; Zurek, E.; Hutchison, G. R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminf. 2012, 4, 17, DOI: 10.1186/1758-2946-4-17Google Scholar223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVGksLg%253D&md5=f10400f51db314afa780e99403ca748aAvogadro: an advanced semantic chemical editor, visualization, and analysis platformHanwell, Marcus D.; Curtis, Donald E.; Lonie, David C.; Vandermeersch, Tim; Zurek, Eva; Hutchison, Geoffrey R.Journal of Cheminformatics (2012), 4 (), 17CODEN: JCOHB3; ISSN:1758-2946. (Chemistry Central Ltd.)Background: The Avogadro project has developed an advanced mol. editor and visualizer designed for cross-platform use in computational chem., mol. modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building mol. structures, formatting input files, and analyzing output of a wide variety of computational chem. packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chem. data types. Results: The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chem., physics, materials science, and biol. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate mol. structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for mol. dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here. Conclusions: Avogadro offers a semantic chem. builder and platform for visualization and anal. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extg. chem. data from a wide variety of formats, including computational chem. output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in org. chem., inorg. complexes, drug design, materials, biomols., and simulations.
- 224NANO-D. INRIA, SAMSON Software, Version ∼0.5.0; http://www.samson-connect.net/, 2016 (Accessed: 09 February 2018).Google ScholarThere is no corresponding record for this reference.
- 225Bosson, M.; Richard, C.; Plet, A.; Grudinin, S.; Redon, S. Interactive Quantum Chemistry: A Divide-and-Conquer ASED-MO Method. J. Comput. Chem. 2012, 33, 779– 790, DOI: 10.1002/jcc.22905Google Scholar225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xkt1Gksw%253D%253D&md5=892979e833f4d542fe8634c28157fd7eInteractive quantum chemistry: A divide-and-conquer ASED-MO methodBosson, Maeel; Richard, Caroline; Plet, Antoine; Grudinin, Sergei; Redon, StephaneJournal of Computational Chemistry (2012), 33 (7), 779-790CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present interactive quantum chem. simulation at the atom superposition and electron delocalization MO (ASED-MO) level of theory. Our method is based on the divide-and-conquer (D and C) approach, which we show is accurate and efficient for this non-self-consistent semiempirical theory. The method has a linear complexity in the no. of atoms, scales well with the no. of cores, and has a small prefactor. The time cost is completely controllable, as all steps are performed with direct algorithms, i.e., no iterative schemes are used. We discuss the errors induced by the D and C approach, first empirically on a few examples, and then via a theor. study of two toy models that can be anal. solved for any no. of atoms. Thanks to the precision and speed of the D and C approach, we are able to demonstrate interactive quantum chem. simulations for systems up to a few hundred atoms on a current multicore desktop computer. When drawing and editing mol. systems, interactive simulations provide immediate, intuitive feedback on chem. structures. As the no. of cores on personal computers increases, and larger and larger systems can be dealt with, we believe such interactive simulations-even at lower levels of theory-should thus prove most useful to effectively understand, design and prototype mols., devices and materials. © 2012 Wiley Periodicals, Inc.
- 226Rossi, R.; Isorce, M.; Morin, S.; Flocard, J.; Arumugam, K.; Crouzy, S.; Vivaudou, M.; Redon, S. Adaptive Torsion-Angle Quasi-Statics: A General Simulation Method with Applications to Protein Structure Analysis and Design. Bioinformatics 2007, 23, i408– i417, DOI: 10.1093/bioinformatics/btm191Google ScholarThere is no corresponding record for this reference.
- 227Bosson, M.; Grudinin, S.; Bouju, X.; Redon, S. Interactive Physically-Based Structural Modeling of Hydrocarbon Systems. J. Comput. Phys. 2012, 231, 2581– 2598, DOI: 10.1016/j.jcp.2011.12.006Google Scholar227https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Ogsbw%253D&md5=597f128c081cf549f0ef8667d746861cInteractive physically-based structural modeling of hydrocarbon systemsBosson, Mael; Grudinin, Sergei; Bouju, Xavier; Redon, StephaneJournal of Computational Physics (2012), 231 (6), 2581-2598CODEN: JCTPAH; ISSN:0021-9991. (Elsevier Inc.)Hydrocarbon systems have been intensively studied via numerical methods, including electronic structure computations, mol. dynamics and Monte Carlo simulations. Typically, these methods require an initial structural model (at. positions and types, topol., etc.) that may be produced using scripts and/or modeling tools. For many systems, however, these building methods may be ineffective, as the user may have to specify the positions of numerous atoms while maintaining structural plausibility. In this paper, we present an interactive phys.-based modeling tool to construct structural models of hydrocarbon systems. As the user edits the geometry of the system, at. positions are also influenced by the Brenner potential, a well-known bond-order reactive potential. In order to be able to interactively edit systems contg. numerous atoms, we introduce a new adaptive simulation algorithm, as well as a novel algorithm to incrementally update the forces and the total potential energy based on the list of updated relative at. positions. The computational cost of the adaptive simulation algorithm depends on user-defined error thresholds, and our potential update algorithm depends linearly with the no. of updated bonds. This allows us to enable efficient phys.-based editing, since the computational cost is decoupled from the no. of atoms in the system. We show that our approach may be used to effectively build realistic models of hydrocarbon structures that would be difficult or impossible to produce using other tools.
- 228Bosson, M.; Grudinin, S.; Redon, S. Block-Adaptive Quantum Mechanics: An Adaptive Divide-and-Conquer Approach to Interactive Quantum Chemistry. J. Comput. Chem. 2013, 34, 492– 504, DOI: 10.1002/jcc.23157Google ScholarThere is no corresponding record for this reference.
- 229Jaillet, L.; Artemova, S.; Redon, S. IM-UFF: Extending the Universal Force Field for Interactive Molecular Modeling. J. Mol. Graphics Modell. 2017, 77, 350– 362, DOI: 10.1016/j.jmgm.2017.08.023Google Scholar229https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFGht7zL&md5=d8a6e882b109aa01ac2ce81758ec234bIM-UFF: Extending the universal force field for interactive molecular modelingJaillet, Leonard; Artemova, Svetlana; Redon, StephaneJournal of Molecular Graphics & Modelling (2017), 77 (), 350-362CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)The universal force field (UFF) is a broadly applicable classical force field that contains parameters for almost every atom type of the periodic table. This force field is non-reactive, i.e. the topol. of the system under study is considered as fixed and no creation or breaking of covalent bonds is possible. This paper introduces interactive modeling-UFF (IM-UFF), an extension of UFF that combines the possibility to significantly modify mol. structures (as with reactive force fields) with a broad diversity of supported systems thanks to the universality of UFF. Such an extension lets the user easily build and edit mol. systems interactively while being guided by physics based inter-at. forces. This approach introduces weighted atom types and weighted bonds, used to update topologies and atom parameterizations at every time step of a simulation. IM-UFF has been evaluated on a large set of benchmarks and is proposed as a self-contained implementation integrated in a new module for the SAMSON software platform for computational nanoscience available at http://www.samson-connect.net.
- 230Disz, T.; Papka, M.; Stevens, R.; Pellegrino, M.; Taylor, V. Virtual Reality Visualization of Parallel Molecular Dynamics Simulation. Proceedings of High-Performance Computing 1995, 483– 487Google ScholarThere is no corresponding record for this reference.
- 231Akkiraju, N.; Edelsbrunner, H.; Fu, P.; Qian, J. Viewing Geometric Protein Structures from inside a CAVE. IEEE Comput. Graph. Appl. 1996, 16, 58– 61, DOI: 10.1109/38.511855Google ScholarThere is no corresponding record for this reference.
- 232Salvadori, A.; Del Frate, G.; Pagliai, M.; Mancini, G.; Barone, V. Immersive Virtual Reality in Computational Chemistry: Applications to the Analysis of QM and MM Data. Int. J. Quantum Chem. 2016, 116, 1731– 1746, DOI: 10.1002/qua.25207Google Scholar232https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFCrurnF&md5=bbfba250da95eba7fbd0583621fcb11dImmersive virtual reality in computational chemistry: Applications to the analysis of QM and MM dataSalvadori, Andrea; Del Frate, Gianluca; Pagliai, Marco; Mancini, Giordano; Barone, VincenzoInternational Journal of Quantum Chemistry (2016), 116 (22), 1731-1746CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)The role of Virtual Reality (VR) tools in mol. sciences is analyzed in this contribution through the presentation of the Caffeine software to the quantum chem. community. Caffeine, developed at Scuola Normale Superiore, is specifically tailored for mol. representation and data visualization with VR systems, such as VR theaters and helmets. Usefulness and advantages that can be gained by exploiting VR are here reported, considering few examples specifically selected to illustrate different level of theory and mol. representation.
- 233García-Hernández, R. J.; Kranzlmüller, D. Virtual Reality Toolset for Material Science: NOMAD VR Tools. Augmented Reality, Virtual Reality, and Computer Graphics . 2017; pp 309– 319.Google ScholarThere is no corresponding record for this reference.
- 234Haase, H.; Strassner, J.; Dai, F. VR Techniques for the Investigation of Molecule Data. Computers & Graphics 1996, 20, 207– 217, DOI: 10.1016/0097-8493(95)00127-1Google ScholarThere is no corresponding record for this reference.
- 235Sauer, C.; Hastings, W.; Okamura, A. M. Virtual Environment for Exploring Atomic Bonding. Proceedings of EuroHaptics 2004; International Design Foundation, 2004; pp 232– 239.Google ScholarThere is no corresponding record for this reference.
- 236Norrby, M.; Grebner, C.; Eriksson, J.; Boström, J. Molecular Rift: Virtual Reality for Drug Designers. J. Chem. Inf. Model. 2015, 55, 2475– 2484, DOI: 10.1021/acs.jcim.5b00544Google Scholar236https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGjurrL&md5=9a206f1ec098ca25df4a6b81f217891fMolecular Rift: Virtual Reality for Drug DesignersNorrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Bostroem, JonasJournal of Chemical Information and Modeling (2015), 55 (11), 2475-2484CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate phys. presence in the real world-a virtual reality. This is relevant to drug discovery since mol. models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Mol. Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for std. input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Mol. Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chem. and education. Mol. Rift is open source and can be downloaded from GitHub.
- 237Harvey, E.; Gingold, C. Haptic Representation of the Atom. 2000 IEEE Conference on Information Visualization. An International Conference on Computer Visualization and Graphics; IEEE, 2000; pp 232– 235.Google ScholarThere is no corresponding record for this reference.
- 238Comai, S.; Mazza, D. A Haptic-Enhanced System for Molecular Sensing. Human-Computer Interaction – INTERACT 2009; Springer, 2009; pp 493– 496.Google ScholarThere is no corresponding record for this reference.
- 239Satoh, H.; Nukada, T.; Akahane, K.; Sato, M. Construction of Basic Haptic Systems for Feeling the Intermolecular Force in Molecular Models. J. Comput. Aided Chem. 2006, 7, 38– 47, DOI: 10.2751/jcac.7.38Google ScholarThere is no corresponding record for this reference.
- 240Stocks, M. B.; Hayward, S.; Laycock, S. D. Interacting with the Biomolecular Solvent Accessible Surface via a Haptic Feedback Device. BMC Struct. Biol. 2009, 9, 69, DOI: 10.1186/1472-6807-9-69Google Scholar240https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjkvVegtw%253D%253D&md5=863ad1d411a653bccac4b93267584afbInteracting with the biomolecular solvent accessible surface via a haptic feedback deviceStocks Matthew B; Hayward Steven; Laycock Stephen DBMC structural biology (2009), 9 (), 69 ISSN:.BACKGROUND: From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. RESULTS: A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. CONCLUSION: By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk), one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water accessibility of the biomolecular surface that cannot be so easily attained using conventional molecular graphics software.
- 241Sankaranarayanan, G.; Weghorst, S.; Sanner, M.; Gillet, A.; Olson, A. Role of Haptics in Teaching Structural Molecular Biology. 11th Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems; IEEE, 2003; pp 363– 366.Google ScholarThere is no corresponding record for this reference.
- 242Persson, P. B.; Cooper, M. D.; Tibell, L. A. E.; Ainsworth, S.; Ynnerman, A.; Jonsson, B. H. Designing and Evaluating a Haptic System for Biomolecular Education. 2007 IEEE Virtual Reality Conference; IEEE, 2007; pp 171– 178.Google ScholarThere is no corresponding record for this reference.
- 243Sourina, O.; Torres, J.; Wang, J. In Transactions on Edutainment II; Pan, Z., Cheok, A. D., Müller, W., Rhalibi, A. E., Eds.; Springer: Berlin, Heidelberg, 2009; Chapter Visual Haptic-Based Biomolecular Docking and Its Applications in E-Learning, pp 105– 118.Google ScholarThere is no corresponding record for this reference.
- 244Bivall, P.; Ainsworth, S.; Tibell, L. A. E. Do Haptic Representations Help Complex Molecular Learning?. Sci. Educ. 2011, 95, 700– 719, DOI: 10.1002/sce.20439Google ScholarThere is no corresponding record for this reference.
- 245Chastine, J. W.; Zhu, Y.; Brooks, J. C.; Owen, G. S.; Harrison, R. W.; Weber, I. T. A Collaborative Multi-View Virtual Environment for Molecular Visualization and Modeling. Coordinated and Multiple Views in Exploratory Visualization; IEEE, 2005; pp 77– 84.Google ScholarThere is no corresponding record for this reference.
- 246Nadan, T.; Haffegee, A.; Watson, K. Collaborative and Parallelized Immersive Molecular Docking. International Conference on Computational Science 2009, 5545, 737– 745, DOI: 10.1007/978-3-642-01973-9_82Google ScholarThere is no corresponding record for this reference.
- 247Hou, X.; Sourina, O.; Klimenko, S. Visual Haptic-Based Collaborative Molecular Docking. IFMBE Proceedings 2014, 43, 360– 363, DOI: 10.1007/978-3-319-02913-9_92Google ScholarThere is no corresponding record for this reference.
- 248Davies, E.; Tew, P.; Glowacki, D.; Smith, J.; Mitchell, T. Evolutionary and Biologically Inspired Music, Sound, Art and Design. Proceedings of the 5th International Conference, EvoMUSART 2016, Porto, Portugal, March 30 – April 1, 2016; Johnson, C., Ciesielski, V., Correia, J. a., Machado, P., Eds.; Springer International Publishing, 2016; pp 17– 30.Google ScholarThere is no corresponding record for this reference.
- 249Mitchell, T.; Hyde, J.; Tew, P.; Glowacki, D. R. Danceroom Spectroscopy: At the Frontiers of Physics, Performance, Interactive Art and Technology. Leonardo 2016, 49, 138– 147, DOI: 10.1162/LEON_a_00924Google ScholarThere is no corresponding record for this reference.
- 250Marti, K. H.; Reiher, M. Haptic Quantum Chemistry. J. Comput. Chem. 2009, 30, 2010– 2020, DOI: 10.1002/jcc.21201Google Scholar250https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXptleqsLw%253D&md5=a0b7305f8d60a1b2a5c8bf5938d6f2a5Haptic quantum chemistryMarti, Konrad H.; Reiher, MarkusJournal of Computational Chemistry (2009), 30 (13), 2010-2020CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present an implementation designed to phys. experience quantum mech. forces between reactants in chem. reactions. This allows one to screen the profile of potential energy surfaces for the study of reaction mechanisms. For this, we have developed a interface between the user and a virtual lab. by means of a force-feedback haptic device. Potential energy surfaces of chem. reactions can be explored efficiently by rendering in the haptic device the gradients calcd. with first-principles methods. The underlying potential energy surface is accurately fitted on the fly by the interpolating moving least-squares (IMLS) scheme to a grid of quantum chem. electronic energies (and geometric gradients). In addn., we introduce a new IMLS-based method to locate min.-energy paths between two points on a potential energy surface. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009.
- 251Haag, M. P.; Marti, K. H.; Reiher, M. Generation of Potential Energy Surfaces in High Dimensions and Their Haptic Exploration. ChemPhysChem 2011, 12, 3204– 3213, DOI: 10.1002/cphc.201100539Google Scholar251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFKrtLjL&md5=df3aa356658e41578110e6b4dd5228aaGeneration of Potential Energy Surfaces in High Dimensions and Their Haptic ExplorationHaag, Moritz P.; Marti, Konrad H.; Reiher, MarkusChemPhysChem (2011), 12 (17), 3204-3213CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)A method is proposed for the automated generation of potential energy surfaces in high dimensions. It combines the existing algorithm for the definition of new energy data points, based on the interpolating moving least-squares algorithm with a simulated annealing procedure. This method is then studied in a haptic quantum chem. environment that requires a fast evaluation of gradients on a potential energy surface with automatic improvement of its accuracy. As an example we investigate the nitrogen binding pathway in the Schrock dinitrogen fixation complex with this set-up.
- 252Haag, M. P.; Reiher, M. Real-Time Quantum Chemistry. Int. J. Quantum Chem. 2013, 113, 8– 20, DOI: 10.1002/qua.24336Google Scholar252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVykt7fP&md5=ec7746303ee168218745cb0b4539fdb9Real-time quantum chemistryHaag, Moritz P.; Reiher, MarkusInternational Journal of Quantum Chemistry (2013), 113 (1), 8-20CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)Significant progress in the development of efficient and fast algorithms for quantum chem. calcns. has been made in the past two decades. The main focus has always been the desire to be able to treat ever larger mols. or mol. assemblies-esp. linear and sublinear scaling techniques are devoted to the accomplishment of this goal. However, as many chem. reactions are rather local, they usually involve only a limited no. of atoms so that models of about 200 (or even less) atoms embedded in a suitable environment are sufficient to study their mechanisms. Thus, the system size does not need to be enlarged, but remains const. for reactions of this type that can be described by less than 200 atoms. The question then arises how fast one can obtain the quantum chem. results. This question is not directly answered by linear-scaling techniques. In fact, ideas such as haptic quantum chem. (HQC) or interactive quantum chem. require an immediate provision of quantum chem. information which demands the calcn. of data in "real time." In this perspective, we aim at a definition of real-time quantum chem., explore its realm and eventually discuss applications in the field of HQC. For the latter, we elaborate whether a direct approach is possible by virtue of real-time quantum chem. © 2012 Wiley Periodicals, Inc.
- 253Haag, M. P.; Reiher, M. Studying Chemical Reactivity in a Virtual Environment. Faraday Discuss. 2014, 169, 89– 118, DOI: 10.1039/C4FD00021HGoogle Scholar253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7nF&md5=8b0b85c38bb608e1d9b8b6fa79ef8760Studying chemical reactivity in a virtual environmentHaag, Moritz P.; Reiher, MarkusFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 89-118CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Chem. reactivity of a set of reactants is detd. by its potential (electronic) energy (hyper)surface. The high dimensionality of this surface renders it difficult to efficiently explore reactivity in a large reactive system. Exhaustive sampling techniques and search algorithms are not straightforward to employ as it is not clear which explored path will eventually produce the min. energy path of a reaction passing through a transition structure. Here, the chemist's intuition would be of invaluable help, but it cannot be easily exploited because (1) no intuitive and direct tool for the scientist to manipulate mol. structures is currently available and because (2) quantum chem. calcns. are inherently expensive in terms of computational effort. In this work, we elaborate on how the chemist can be reintroduced into the exploratory process within a virtual environment that provides immediate feedback and intuitive tools to manipulate a reactive system. We work out in detail how this immersion should take place. We provide an anal. of modern semi-empirical methods which already today are candidates for the interactive study of chem. reactivity. Implications of manual structure manipulations for their phys. meaning and chem. relevance are carefully analyzed in order to provide sound theor. foundations for the interpretation of the interactive reactivity exploration.
- 254Haag, M. P.; Vaucher, A. C.; Bosson, M.; Redon, S.; Reiher, M. Interactive Chemical Reactivity Exploration. ChemPhysChem 2014, 15, 3301– 3319, DOI: 10.1002/cphc.201402342Google Scholar254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSgsrnM&md5=5c26a58bb25aa70f7a71ebf0c93ea3ccInteractive Chemical Reactivity ExplorationHaag, Moritz P.; Vaucher, Alain C.; Bosson, Mael; Redon, Stephane; Reiher, MarkusChemPhysChem (2014), 15 (15), 3301-3319CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)Elucidating chem. reactivity in complex mol. assemblies of a few hundred atoms is, despite the remarkable progress in quantum chem., still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chem. reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mech. response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which tech. difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the SAMSON programming environment.
- 255Mühlbach, A. H.; Vaucher, A. C.; Reiher, M. Accelerating Wave Function Convergence in Interactive Quantum Chemical Reactivity Studies. J. Chem. Theory Comput. 2016, 12, 1228– 1235, DOI: 10.1021/acs.jctc.5b01156Google ScholarThere is no corresponding record for this reference.
- 256Atsumi, T.; Nakai, H. Molecular Orbital Propagation to Accelerate Self-Consistent-Field Convergence in an Ab Initio Molecular Dynamics Simulation. J. Chem. Phys. 2008, 128, 094101, DOI: 10.1063/1.2839857Google Scholar256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjtl2qt74%253D&md5=1b02d7ccbc0390afd6bc6421fe3d2f36Molecular orbital propagation to accelerate self-consistent-field convergence in an ab initio molecular dynamics simulationAtsumi, Teruo; Nakai, HiromiJournal of Chemical Physics (2008), 128 (9), 094101/1-094101/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Based on the idea of MO propagation, we propose a novel effective method for predicting initial guesses for the self-consistent-field calcns. in direct ab initio mol. dynamics (AIMD) simulations. This method, called LIMO, adopts the Lagrange interpolation (LI) polynomial technique and predicts initial MO coeffs. at the next AIMD step by using several previous results. Taking into account the crossing and/or mixing of MOs leads to orbital invariant formulas for the LIMO method. We also propose a simple method for detg. the optimal degree of the LI polynomial, which corresponds to the no. of previous steps. Numerical tests confirm that this proposed method is both effective and feasible. (c) 2008 American Institute of Physics.
- 257Atsumi, T.; Nakai, H. Acceleration of Self-Consistent-Field Convergence in Ab Initio Molecular Dynamics and Monte Carlo Simulations and Geometry Optimization. Chem. Phys. Lett. 2010, 490, 102– 108, DOI: 10.1016/j.cplett.2010.03.012Google Scholar257https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkt1ygt74%253D&md5=378feecb4e22a46ab096a8c43c0e5a9eAcceleration of self-consistent-field convergence in ab initio molecular dynamics and Monte Carlo simulations and geometry optimizationAtsumi, Teruo; Nakai, HiromiChemical Physics Letters (2010), 490 (1-3), 102-108CODEN: CHPLBC; ISSN:0009-2614. (Elsevier B.V.)We propose a novel acceleration method for self-consistent-field calcns. in direct ab initio mol. dynamics/Monte Carlo (AIMD/AIMC) simulations and geometry optimization. This acceleration method, so-called LSMO, predicts an initial guess of MOs (MOs) for the next simulation step by using the geometric information with the least-squares technique. Numerical tests confirm that the LSMO method is both effective and feasible in the AIMD/AIMC simulations and geometry optimization.
- 258Vaucher, A. C.; Haag, M. P.; Reiher, M. Real-Time Feedback from Iterative Electronic Structure Calculations. J. Comput. Chem. 2016, 37, 805– 812, DOI: 10.1002/jcc.24268Google Scholar258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVCltLrK&md5=847dceab1dfd98f653c508db8961b9adReal-time feedback from iterative electronic structure calculationsVaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Computational Chemistry (2016), 37 (9), 805-812CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Real-time feedback from iterative electronic structure calcns. requires to mediate between the inherently unpredictable execution times of the iterative algorithm used and the necessity to provide data in fixed and short time intervals for real-time rendering. We introduce the concept of a mediator as a component able to deal with infrequent and unpredictable ref. data to generate reliable feedback. In the context of real-time quantum chem., the mediator takes the form of a surrogate potential that has the same local shape as the first-principles potential and can be evaluated efficiently to deliver at. forces as real-time feedback. The surrogate potential is updated continuously by electronic structure calcns. and guarantees to provide a reliable response to the operator for any mol. structure. To demonstrate the application of iterative electronic structure methods in real-time reactivity exploration, we implement self-consistent semiempirical methods as the data source and apply the surrogate-potential mediator to deliver reliable real-time feedback. © 2015 Wiley Periodicals, Inc.
- 259Vaucher, A. C.; Reiher, M. Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower Energy. J. Chem. Theory Comput. 2017, 13, 1219– 1228, DOI: 10.1021/acs.jctc.7b00011Google Scholar259https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivVKqs78%253D&md5=94b5a248bcc23b8c0d0e71e82c8be2f1Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower EnergyVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (3), 1219-1228CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The general procedure underlying Hartree-Fock and Kohn-Sham d. functional theory calcns. consists in optimizing orbitals for a self-consistent soln. of the Roothaan-Hall equations in an iterative process. It is often ignored that multiple self-consistent solns. can exist, several of which may correspond to min. of the energy functional. In addn. to the difficulty sometimes encountered to converge the calcn. to a self-consistent soln., one must ensure that the correct self-consistent soln. was found, typically the one with the lowest electronic energy. Convergence to an unwanted soln. is in general not trivial to detect and will deliver incorrect energy and mol. properties and accordingly a misleading description of chem. reactivity. Wrong conclusions based on incorrect SCF convergence are particularly cumbersome in automated calcns. met in high-throughput virtual screening, structure optimizations, ab initio mol. dynamics, and in real-time explorations of chem. reactivity, where the vast amt. of data can hardly be manually inspected. Here, we introduce a fast and automated approach to detect and cure incorrect orbital convergence, which is esp. suited for electronic structure calcns. on sequences of mol. structures. Our approach consists of a randomized perturbation of the converged electron d. (matrix) intended to push orbital convergence to solns. that correspond to another stationary point (of potentially lower electronic energy) in the variational parameter space of an electronic wave function approxn.
- 260Vaucher, A. C.; Reiher, M. Molecular Propensity as a Driver for Explorative Reactivity Studies. J. Chem. Inf. Model. 2016, 56, 1470– 1478, DOI: 10.1021/acs.jcim.6b00264Google Scholar260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xht1WntbrN&md5=ba5071e8f71e85291382737cf389899aMolecular Propensity as a Driver for Explorative Reactivity StudiesVaucher, Alain C.; Reiher, MarkusJournal of Chemical Information and Modeling (2016), 56 (8), 1470-1478CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Quantum chem. studies of reactivity involve calcns. on a large no. of mol. structures and the comparison of their energies. Already the setup of these calcns. limits the scope of the results that one will obtain, because several system-specific variables such as the charge and spin need to be set prior to the calcn. For a reliable exploration of reaction mechanisms, a considerable no. of calcns. with varying global parameters must be taken into account, or important facts about the reactivity of the system under consideration can remain undetected. For example, one could miss crossings of potential energy surfaces for different spin states or might not note that a mol. is prone to oxidn. Here, we introduce the concept of mol. propensity to account for the predisposition of a mol. system to react across different electronic states in certain nuclear configurations or with other reactants present in the reaction liquor. Within our real-time quantum chem. framework, we developed an algorithm that automatically detects and flags such a propensity of a system under consideration.
- 261Heuer, M. A.; Vaucher, A. C.; Haag, M. P.; Reiher, M. Integrated Reaction Path Processing from Sampled Structure Sequences. J. Chem. Theory Comput. 2018, 14, 2052– 2062, DOI: 10.1021/acs.jctc.8b00019Google Scholar261https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXktFWgs78%253D&md5=aa7c203a39a0cc9c876174b2c517e4c5Integrated Reaction Path Processing from Sampled Structure SequencesHeuer, Michael A.; Vaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (4), 2052-2062CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Sampled structure sequences obtained, for instance, from real-time reactivity explorations or first-principles mol. dynamics simulations contain valuable information about chem. reactivity. Eventually, such sequences allow for the construction of reaction networks that are required for the kinetic anal. of chem. systems. For this purpose, however, the sampled information must be processed to obtain stable chem. structures and assocd. transition states. The manual extn. of valuable information from such reaction paths is straightforward but unfeasible for large and complex reaction networks. For real-time quantum chem., this implies automatization of the extn. and relaxation process while maintaining immersion in the virtual chem. environment. Here, we describe an efficient path processing scheme for the on-the-fly construction of an exploration network by approximating the explored paths as continuous basis-spline curves.
- 262Reiher, M.; SCINE – Software for Chemical Interaction Networks. http://scine.ethz.ch (Accessed: 12. September 2018).Google ScholarThere is no corresponding record for this reference.
Cited By
Click to copy section linkSection link copied!
This article is cited by 159 publications.
- Jan A. Meissner, Jan Meisner. Acceleration of Diffusion in Ab Initio Nanoreactor Molecular Dynamics and Application to Hydrogen Sulfide Oxidation. Journal of Chemical Theory and Computation 2024, Article ASAP.化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Charlotte H. Müller, Miguel Steiner, Jan P. Unsleber, Thomas Weymuth, Moritz Bensberg, Katja-Sophia Csizi, Maximilian Mörchen, Paul L. Türtscher, Markus Reiher. Heron: Visualizing and Controlling Chemical Reaction Explorations and Networks. The Journal of Physical Chemistry A 2024, 128
(41)
, 9028-9044. https://doi.org/10.1021/acs.jpca.4c03936EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Miko M. Stulajter, Dmitrij Rappoport. Reaction Networks Resemble Low-Dimensional Regular Lattices. Journal of Chemical Theory and Computation 2024, 20
(18)
, 8035-8048. https://doi.org/10.1021/acs.jctc.4c00810化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Karthik Srinivasan, Anjana Puliyanda, Vinay Prasad. Identification of Reaction Network Hypotheses for Complex Feedstocks from Spectroscopic Measurements with Minimal Human Intervention. The Journal of Physical Chemistry A 2024, 128
(23)
, 4714-4729. https://doi.org/10.1021/acs.jpca.4c01592EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Moritz Bensberg, Markus Reiher. Uncertainty-Aware First-Principles Exploration of Chemical Reaction Networks. The Journal of Physical Chemistry A 2024, 128
(22)
, 4532-4547. https://doi.org/10.1021/acs.jpca.3c08386EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Yuheng Ding, Bo Qiang, Qixuan Chen, Yiqiao Liu, Liangren Zhang, Zhenming Liu. Exploring Chemical Reaction Space with Machine Learning Models: Representation and Feature Perspective. Journal of Chemical Information and Modeling 2024, 64
(8)
, 2955-2970. https://doi.org/10.1021/acs.jcim.4c00004化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Yu Harabuchi, Tomohiko Yokoyama, Wataru Matsuoka, Taihei Oki, Satoru Iwata, Satoshi Maeda. Differentiating the Yield of Chemical Reactions Using Parameters in First-Order Kinetic Equations to Identify Elementary Steps That Control the Reactivity from Complicated Reaction Path Networks. The Journal of Physical Chemistry A 2024, 128
(14)
, 2883-2890. https://doi.org/10.1021/acs.jpca.4c00204EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Yutai Zhang, Chao Xu, Zhenggang Lan. Automated Exploration of Reaction Networks and Mechanisms Based on Metadynamics Nanoreactor Simulations. Journal of Chemical Theory and Computation 2023, 19
(23)
, 8718-8731. https://doi.org/10.1021/acs.jctc.3c00752化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Taisuke Hasegawa, Satoshi Hagiwara, Minoru Otani, Satoshi Maeda. A Combined Reaction Path Search and Hybrid Solvation Method for the Systematic Exploration of Elementary Reactions at the Solid–Liquid Interface. The Journal of Physical Chemistry Letters 2023, 14
(39)
, 8796-8804. https://doi.org/10.1021/acs.jpclett.3c02233化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 4.8SWJTU A++
- Jan P. Unsleber. Accelerating Reaction Network Explorations with Automated Reaction Template Extraction and Application. Journal of Chemical Information and Modeling 2023, 63
(11)
, 3392-3403. https://doi.org/10.1021/acs.jcim.3c00102化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Wataru Matsuoka, Yu Harabuchi, Satoshi Maeda. Virtual Ligand Strategy in Transition Metal Catalysis Toward Highly Efficient Elucidation of Reaction Mechanisms and Computational Catalyst Design. ACS Catalysis 2023, 13
(8)
, 5697-5711. https://doi.org/10.1021/acscatal.3c00576化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Atsuyuki Nakao, Yu Harabuchi, Satoshi Maeda, Koji Tsuda. Exploring the Quantum Chemical Energy Landscape with GNN-Guided Artificial Force. Journal of Chemical Theory and Computation 2023, 19
(3)
, 713-717. https://doi.org/10.1021/acs.jctc.2c01061化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Judit Zádor, Carles Martí, Ruben Van de Vijver, Sommer L. Johansen, Yoona Yang, Hope A. Michelsen, Habib N. Najm. Automated Reaction Kinetics of Gas-Phase Organic Species over Multiwell Potential Energy Surfaces. The Journal of Physical Chemistry A 2023, 127
(3)
, 565-588. https://doi.org/10.1021/acs.jpca.2c06558EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Bastian Bjerkem Skjelstad, Yuh Hijikata, Satoshi Maeda. Early-Stage Formation of the SIFSIX-3-Zn Metal–Organic Framework: An Automated Computational Study. Inorganic Chemistry 2023, 62
(3)
, 1210-1217. https://doi.org/10.1021/acs.inorgchem.2c03681化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 4.3SWJTU A++
- Paul L. Türtscher, Markus Reiher. Pathfinder─Navigating and Analyzing Chemical Reaction Networks with an Efficient Graph-Based Approach. Journal of Chemical Information and Modeling 2023, 63
(1)
, 147-160. https://doi.org/10.1021/acs.jcim.2c01136化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Tsuyoshi Mita, Hideaki Takano, Hiroki Hayashi, Wataru Kanna, Yu Harabuchi, K. N. Houk, Satoshi Maeda. Prediction of High-Yielding Single-Step or Cascade Pericyclic Reactions for the Synthesis of Complex Synthetic Targets. Journal of the American Chemical Society 2022, 144
(50)
, 22985-23000. https://doi.org/10.1021/jacs.2c09830化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Stefan Gugler, Markus Reiher. Quantum Chemical Roots of Machine-Learning Molecular Similarity Descriptors. Journal of Chemical Theory and Computation 2022, 18
(11)
, 6670-6689. https://doi.org/10.1021/acs.jctc.2c00718化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Alexandra Stan, Beatriz von der Esch, Christian Ochsenfeld. Fully Automated Generation of Prebiotically Relevant Reaction Networks from Optimized Nanoreactor Simulations. Journal of Chemical Theory and Computation 2022, 18
(11)
, 6700-6712. https://doi.org/10.1021/acs.jctc.2c00754化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Umberto Raucci, David M. Sanchez, Todd J. Martínez, Michele Parrinello. Enhanced Sampling Aided Design of Molecular Photoswitches. Journal of the American Chemical Society 2022, 144
(42)
, 19265-19271. https://doi.org/10.1021/jacs.2c04419化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Idil Ismail, Raphael Chantreau Majerus, Scott Habershon. Graph-Driven Reaction Discovery: Progress, Challenges, and Future Opportunities. The Journal of Physical Chemistry A 2022, 126
(40)
, 7051-7069. https://doi.org/10.1021/acs.jpca.2c06408EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Philipp Pracht, Christoph Bannwarth. Fast Screening of Minimum Energy Crossing Points with Semiempirical Tight-Binding Methods. Journal of Chemical Theory and Computation 2022, 18
(10)
, 6370-6385. https://doi.org/10.1021/acs.jctc.2c00578化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Bastian Bjerkem Skjelstad, Trygve Helgaker, Satoshi Maeda, David Balcells. Oxyl Character and Methane Hydroxylation Mechanism in Heterometallic M(O)Co3O4 Cubanes (M = Cr, Mn, Fe, Mo, Tc, Ru, and Rh). ACS Catalysis 2022, 12
(19)
, 12326-12335. https://doi.org/10.1021/acscatal.2c03748化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Jan P. Unsleber, Stephanie A. Grimmel, Markus Reiher. Chemoton 2.0: Autonomous Exploration of Chemical Reaction Networks. Journal of Chemical Theory and Computation 2022, 18
(9)
, 5393-5409. https://doi.org/10.1021/acs.jctc.2c00193化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Qinxuan Wang, Jiun-Le Shih, Ka Yi Tsui, Croix J. Laconsay, Dean J. Tantillo, Jeremy A. May. Experimental and Computational Mechanistic Study of Carbonazidate-Initiated Cascade Reactions. The Journal of Organic Chemistry 2022, 87
(14)
, 8983-9000. https://doi.org/10.1021/acs.joc.2c00696EI检索SCI升级版 化学2区SCI基础版 化学2区IF 3.3
- Diego Garay-Ruiz, Moises Álvarez-Moreno, Carles Bo, Emilio Martínez-Núñez. New Tools for Taming Complex Reaction Networks: The Unimolecular Decomposition of Indole Revisited. ACS Physical Chemistry Au 2022, 2
(3)
, 225-236. https://doi.org/10.1021/acsphyschemau.1c00051IF 3.7
- Lin Ji, Yue Li, Jie Wang, An Ning, Naixin Zhang, Shengyao Liang, Jiyun He, Tianyu Zhang, Zexing Qu, Jiali Gao. Community Reaction Network Reduction for Constructing a Coarse-Grained Representation of Combustion Reaction Mechanisms. Journal of Chemical Information and Modeling 2022, 62
(10)
, 2352-2364. https://doi.org/10.1021/acs.jcim.2c00240化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Yosuke Sumiya, Yu Harabuchi, Yuuya Nagata, Satoshi Maeda. Quantum Chemical Calculations to Trace Back Reaction Paths for the Prediction of Reactants. JACS Au 2022, 2
(5)
, 1181-1188. https://doi.org/10.1021/jacsau.2c00157IF 8.5
- Xin Chen, Meiyi Liu, Jiali Gao. CARNOT: a Fragment-Based Direct Molecular Dynamics and Virtual–Reality Simulation Package for Reactive Systems. Journal of Chemical Theory and Computation 2022, 18
(3)
, 1297-1313. https://doi.org/10.1021/acs.jctc.1c01032化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Lukas Krep, Indu Sekhar Roy, Wassja Kopp, Felix Schmalz, Can Huang, Kai Leonhard. Efficient Reaction Space Exploration with ChemTraYzer-TAD. Journal of Chemical Information and Modeling 2022, 62
(4)
, 890-902. https://doi.org/10.1021/acs.jcim.1c01197化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Alberto Baiardi, Stephanie A. Grimmel, Miguel Steiner, Paul L. Türtscher, Jan P. Unsleber, Thomas Weymuth, Markus Reiher. Expansive Quantum Mechanical Exploration of Chemical Reaction Paths. Accounts of Chemical Research 2022, 55
(1)
, 35-43. https://doi.org/10.1021/acs.accounts.1c00472化学TOPSCI升级版 化学1区SCI基础版 化学1区IF 16.4
- Craig Waitt, Audrey R. Miles, William F. Schneider. Adsorbate Free Energies from DFT-Derived Translational Energy Landscapes. The Journal of Physical Chemistry C 2021, 125
(37)
, 20331-20342. https://doi.org/10.1021/acs.jpcc.1c05917EI检索SCI升级版 化学3区SCI基础版 化学2区IF 3.3SWJTU A++
- Victoria P. Barber, William H. Green, Jesse H. Kroll. Screening for New Pathways in Atmospheric Oxidation Chemistry with Automated Mechanism Generation. The Journal of Physical Chemistry A 2021, 125
(31)
, 6772-6788. https://doi.org/10.1021/acs.jpca.1c04297EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Robin J. Shannon, Emilio Martínez-Núñez, Dmitrii V. Shalashilin, David R. Glowacki. ChemDyME: Kinetically Steered, Automated Mechanism Generation through Combined Molecular Dynamics and Master Equation Calculations. Journal of Chemical Theory and Computation 2021, 17
(8)
, 4901-4912. https://doi.org/10.1021/acs.jctc.1c00335化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Christoph Brunken, Markus Reiher. Automated Construction of Quantum–Classical Hybrid Models. Journal of Chemical Theory and Computation 2021, 17
(6)
, 3797-3813. https://doi.org/10.1021/acs.jctc.1c00178化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Christopher Robertson, Ross Hyland, Andrew J. D. Lacey, Sebastian Havens, Scott Habershon. Identifying Barrierless Mechanisms for Benzene Formation in the Interstellar Medium Using Permutationally Invariant Reaction Discovery. Journal of Chemical Theory and Computation 2021, 17
(4)
, 2307-2322. https://doi.org/10.1021/acs.jctc.1c00046化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Thijs Stuyver, Sason Shaik. Promotion Energy Analysis Predicts Reaction Modes: Nucleophilic and Electrophilic Aromatic Substitution Reactions. Journal of the American Chemical Society 2021, 143
(11)
, 4367-4378. https://doi.org/10.1021/jacs.1c00307化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Timur Gimadiev, Ramil Nugmanov, Dinar Batyrshin, Timur Madzhidov, Satoshi Maeda, Pavel Sidorov, Alexandre Varnek. Combined Graph/Relational Database Management System for Calculated Chemical Reaction Pathway Data. Journal of Chemical Information and Modeling 2021, 61
(2)
, 554-559. https://doi.org/10.1021/acs.jcim.0c01280化学TOPEI检索SCI升级版 化学2区SCI基础版 化学2区IF 5.6
- Ali Hussain Motagamwala, James A. Dumesic. Microkinetic Modeling: A Tool for Rational Catalyst Design. Chemical Reviews 2021, 121
(2)
, 1049-1076. https://doi.org/10.1021/acs.chemrev.0c00394化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 51.4
- Yu-hong Lam, Yuriy Abramov, Ravi S. Ananthula, Jennifer M. Elward, Lori R. Hilden, Sten O. Nilsson Lill, Per-Ola Norrby, Antonio Ramirez, Edward C. Sherer, Jason Mustakis, Gerald J. Tanoury. Applications of Quantum Chemistry in Pharmaceutical Process Development: Current State and Opportunities. Organic Process Research & Development 2020, 24
(8)
, 1496-1507. https://doi.org/10.1021/acs.oprd.0c00222EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.1
- Christoph Brunken, Markus Reiher. Self-Parametrizing System-Focused Atomistic Models. Journal of Chemical Theory and Computation 2020, 16
(3)
, 1646-1665. https://doi.org/10.1021/acs.jctc.9b00855化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Sebastian Dohm, Markus Bursch, Andreas Hansen, Stefan Grimme. Semiautomated Transition State Localization for Organometallic Complexes with Semiempirical Quantum Chemical Methods. Journal of Chemical Theory and Computation 2020, 16
(3)
, 2002-2012. https://doi.org/10.1021/acs.jctc.9b01266化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Marco Foscato, Vidar R. Jensen. Automated in Silico Design of Homogeneous Catalysts. ACS Catalysis 2020, 10
(3)
, 2354-2377. https://doi.org/10.1021/acscatal.9b04952化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Pei-Lin Kang, Cheng Shang, Zhi-Pan Liu. Glucose to 5-Hydroxymethylfurfural: Origin of Site-Selectivity Resolved by Machine Learning Based Reaction Sampling. Journal of the American Chemical Society 2019, 141
(51)
, 20525-20536. https://doi.org/10.1021/jacs.9b11535化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 14.4SWJTU A++
- Eric D. Hermes, Khachik Sargsyan, Habib N. Najm, Judit Zádor. Accelerated Saddle Point Refinement through Full Exploitation of Partial Hessian Diagonalization. Journal of Chemical Theory and Computation 2019, 15
(11)
, 6536-6549. https://doi.org/10.1021/acs.jctc.9b00869化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Valerio Rizzi, Dan Mendels, Emilia Sicilia, Michele Parrinello. Blind Search for Complex Chemical Pathways Using Harmonic Linear Discriminant Analysis. Journal of Chemical Theory and Computation 2019, 15
(8)
, 4507-4515. https://doi.org/10.1021/acs.jctc.9b00358化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Sebastian Matera, William F. Schneider, Andreas Heyden, Aditya Savara. Progress in Accurate Chemical Kinetic Modeling, Simulations, and Parameter Estimation for Heterogeneous Catalysis. ACS Catalysis 2019, 9
(8)
, 6624-6647. https://doi.org/10.1021/acscatal.9b01234化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.3
- Dmitrij Rappoport, Alán Aspuru-Guzik. Predicting Feasible Organic Reaction Pathways Using Heuristically Aided Quantum Chemistry. Journal of Chemical Theory and Computation 2019, 15
(7)
, 4099-4112. https://doi.org/10.1021/acs.jctc.9b00126化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Jin Woo Kim, Yeonjoon Kim, Kyung Yup Baek, Kyunghoon Lee, Woo Youn Kim. Performance of ACE-Reaction on 26 Organic Reactions for Fully Automated Reaction Network Construction and Microkinetic Analysis. The Journal of Physical Chemistry A 2019, 123
(22)
, 4796-4805. https://doi.org/10.1021/acs.jpca.9b02161EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Stefan Grimme. Exploration of Chemical Compound, Conformer, and Reaction Space with Meta-Dynamics Simulations Based on Tight-Binding Quantum Chemical Calculations. Journal of Chemical Theory and Computation 2019, 15
(5)
, 2847-2862. https://doi.org/10.1021/acs.jctc.9b00143化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Idil Ismail, Holly B. V. A. Stuttaford-Fowler, Curtis Ochan Ashok, Christopher Robertson, Scott Habershon. Automatic Proposal of Multistep Reaction Mechanisms using a Graph-Driven Search. The Journal of Physical Chemistry A 2019, 123
(15)
, 3407-3417. https://doi.org/10.1021/acs.jpca.9b01014EI检索SCI升级版 化学2区SCI基础版 化学3区IF 2.7SWJTU A++
- Satoshi Maeda, Yu Harabuchi. On Benchmarking of Automated Methods for Performing Exhaustive Reaction Path Search. Journal of Chemical Theory and Computation 2019, 15
(4)
, 2111-2115. https://doi.org/10.1021/acs.jctc.8b01182化学TOPSCI升级版 化学1区SCI基础版 化学2区IF 5.7SWJTU A++
- Pedro J. Sánchez Gómez, Mauricio Suárez. Plurality and identity: on the educational relations between chemistry and physics. Chemistry Education Research and Practice 2025, https://doi.org/10.1039/D4RP00288ASCI升级版 教育学2区SCI基础版 化学4区IF 2.6
- Seonghwan Kim, Jeheon Woo, Woo Youn Kim. Diffusion-based generative AI for exploring transition states from 2D molecular graphs. Nature Communications 2024, 15
(1)
https://doi.org/10.1038/s41467-023-44629-6综合性期刊TOPSCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Miguel Steiner, Markus Reiher. A human-machine interface for automatic exploration of chemical reaction networks. Nature Communications 2024, 15
(1)
https://doi.org/10.1038/s41467-024-47997-9综合性期刊TOPSCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Katja-Sophia Csizi, Miguel Steiner, Markus Reiher. Nanoscale chemical reaction exploration with a quantum magnifying glass. Nature Communications 2024, 15
(1)
https://doi.org/10.1038/s41467-024-49594-2综合性期刊TOPSCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Basudev Maity, Mitsuo Shoji, Fangjia Luo, Takanori Nakane, Satoshi Abe, Shigeki Owada, Jungmin Kang, Kensuke Tono, Rie Tanaka, Thuc Toan Pham, Mariko Kojima, Yuki Hishikawa, Junko Tanaka, Jiaxin Tian, Misaki Nagama, Taiga Suzuki, Hiroki Noya, Yuto Nakasuji, Asuka Asanuma, Xinchen Yao, So Iwata, Yasuteru Shigeta, Eriko Nango, Takafumi Ueno. Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography. Nature Communications 2024, 15
(1)
https://doi.org/10.1038/s41467-024-49814-9综合性期刊TOPSCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Jonathan P. Mailoa, Xin Li, Shengyu Zhang. 3T-VASP: fast ab-initio electrochemical reactor via multi-scale gradient energy minimization. Nature Communications 2024, 15
(1)
https://doi.org/10.1038/s41467-024-54453-1综合性期刊TOPSCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 14.7SWJTU A++
- Nils van Staalduinen, Christoph Bannwarth. MolBar: a molecular identifier for inorganic and organic molecules with full support of stereoisomerism. Digital Discovery 2024, 3
(11)
, 2298-2319. https://doi.org/10.1039/D4DD00208CIF 6.2
- Thijs Stuyver. TS‐tools: Rapid and automated localization of transition states based on a textual reaction SMILES input. Journal of Computational Chemistry 2024, 45
(27)
, 2308-2317. https://doi.org/10.1002/jcc.27374EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.4SWJTU A++
- Khaled Kahouli, Stefaan Simon Pierre Hessmann, Klaus-Robert Müller, Shinichi Nakajima, Stefan Gugler, Niklas Wolf Andreas Gebauer. Molecular relaxation by reverse diffusion with time step prediction. Machine Learning: Science and Technology 2024, 5
(3)
, 035038. https://doi.org/10.1088/2632-2153/ad652cEI检索SCI升级版 物理与天体物理2区IF 6.3
- Philippe Gantzer, Ruben Staub, Yu Harabuchi, Satoshi Maeda, Alexandre Varnek. Chemography‐guided analysis of a reaction path network for ethylene hydrogenation with a model Wilkinson's catalyst. Molecular Informatics 2024, https://doi.org/10.1002/minf.202400063EI检索SCI升级版 医学4区SCI基础版 医学3区IF 2.8SWJTU A
- Luís P. Viegas, Breno R.L. Galvão. With a little help from our (AI) friend: A general transition state sampling method for tropospheric hydrogen abstraction reactions. Atmospheric Environment 2024, 328 , 120515. https://doi.org/10.1016/j.atmosenv.2024.120515EI检索SCI升级版 环境科学与生态学2区SCI基础版 环境科学与生态学2区IF 4.2
- Raquel J. Rama, Ainara Nova, M. Carmen Nicasio. Microkinetic Model as a Crucial Tool for Understanding Homogeneous Catalysis. ChemCatChem 2024, 65 https://doi.org/10.1002/cctc.202400224EI检索SCI升级版 化学3区SCI基础版 化学2区IF 3.8SWJTU A++
- Daniele Padula. A Computational Perspective on the Reactivity of
π
‐spacers in Self‐Immolative Elimination Reactions. Chemistry – An Asian Journal 2024, 19
(7)
https://doi.org/10.1002/asia.202400010EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.5
- G. Ya. Gerasimov, V. Yu. Levashov. Kinetic Models of Combustion of Kerosene. Journal of Engineering Physics and Thermophysics 2024, 97
(2)
, 506-524. https://doi.org/10.1007/s10891-024-02918-xEI检索IF 0.6
- W.M.C. Sameera, Yosuke Sumiya, Bastian Bjerkem Skjelstad, Satoshi Maeda. Automated Mechanism Discovery. 2024, 454-484. https://doi.org/10.1016/B978-0-12-821978-2.00003-9
- Thomas Weymuth, Markus Reiher. Heuristics and Uncertainty Quantification in Rational and Inverse Compound and Catalyst Design. 2024, 485-495. https://doi.org/10.1016/B978-0-12-821978-2.00007-6
- Valeria Butera. Density functional theory methods applied to homogeneous and heterogeneous catalysis: a short review and a practical user guide. Physical Chemistry Chemical Physics 2024, 136 https://doi.org/10.1039/D4CP00266KEI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.9SWJTU A++
- Chenru Duan, Yuanqi Du, Haojun Jia, Heather J. Kulik. Accurate transition state generation with an object-aware equivariant elementary reaction diffusion model. Nature Computational Science 2023, 3
(12)
, 1045-1055. https://doi.org/10.1038/s43588-023-00563-7EI检索IF 12.0
- Hiroki Hayashi, Satoshi Maeda, Tsuyoshi Mita. Quantum chemical calculations for reaction prediction in the development of synthetic methodologies. Chemical Science 2023, 14
(42)
, 11601-11616. https://doi.org/10.1039/D3SC03319H化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Kyunghoon Lee, Jun Hyeong Kim, Woo Youn Kim. pyMCD: Python package for searching transition states via the multicoordinate driven method. Computer Physics Communications 2023, 291 , 108831. https://doi.org/10.1016/j.cpc.2023.108831EI检索SCI升级版 物理与天体物理2区SCI基础版 物理2区IF 7.2SWJTU A++
- Qiyuan Zhao, Brett M. Savoie. Deep reaction network exploration of glucose pyrolysis. Proceedings of the National Academy of Sciences 2023, 120
(34)
https://doi.org/10.1073/pnas.2305884120综合性期刊TOPSCI升级版 综合性期刊1区SCI基础版 综合性期刊1区IF 9.4SWJTU A++
- Mikael Kuwahara, Yu Harabuchi, Satoshi Maeda, Jun Fujima, Keisuke Takahashi. Searching chemical action and network (SCAN): an interactive chemical reaction path network platform. Digital Discovery 2023, 2
(4)
, 1104-1111. https://doi.org/10.1039/D3DD00026EIF 6.2
- G. Ya. Gerasimov, V. Yu. Levashov. Kinetic Models of Gasoline Combustion. Russian Journal of Physical Chemistry B 2023, 17
(4)
, 923-935. https://doi.org/10.1134/S1990793123040231SCI升级版 化学4区SCI基础版 化学4区IF 1.4SWJTU A
- Г. Я. Герасимов, В. Ю. Левашов. Кинетические модели горения бензина. Химическая физика 2023, 42
(8)
, 12-26. https://doi.org/10.31857/S0207401X23080046SWJTU A
- Mohamed Ateia, Gabriel Sigmund, Michael J. Bentel, John W. Washington, Adelene Lai, Nathaniel H. Merrill, Zhanyun Wang. Integrated data-driven cross-disciplinary framework to prevent chemical water pollution. One Earth 2023, 6
(8)
, 952-963. https://doi.org/10.1016/j.oneear.2023.07.001环境科学与生态学TOPSCI升级版 环境科学与生态学1区IF 15.1
- Rui Xu, Jan Meisner, Alexander M. Chang, Keiran C. Thompson, Todd J. Martínez. First principles reaction discovery: from the Schrodinger equation to experimental prediction for methane pyrolysis. Chemical Science 2023, 14
(27)
, 7447-7464. https://doi.org/10.1039/D3SC01202F化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Katja‐Sophia Csizi, Markus Reiher. Universal
QM
/
MM
approaches for general nanoscale applications. WIREs Computational Molecular Science 2023, 13
(4)
https://doi.org/10.1002/wcms.1656
- Alessandra Toniato, Jan P. Unsleber, Alain C. Vaucher, Thomas Weymuth, Daniel Probst, Teodoro Laino, Markus Reiher. Quantum chemical data generation as fill-in for reliability enhancement of machine-learning reaction and retrosynthesis planning. Digital Discovery 2023, 2
(3)
, 663-673. https://doi.org/10.1039/D3DD00006KIF 6.2
- Satoshi Maeda, Yu Harabuchi, Hiroki Hayashi, Tsuyoshi Mita. Toward Ab Initio Reaction Discovery Using the Artificial Force Induced Reaction Method. Annual Review of Physical Chemistry 2023, 74
(1)
, 287-311. https://doi.org/10.1146/annurev-physchem-102822-101025EI检索SCI升级版 化学1区SCI基础版 化学1区IF 11.7
- Wataru Matsuoka, Yu Harabuchi, Yuuya Nagata, Satoshi Maeda. Highly chemoselective ligands for Suzuki–Miyaura cross-coupling reaction based on virtual ligand-assisted screening. Organic & Biomolecular Chemistry 2023, 21
(15)
, 3132-3142. https://doi.org/10.1039/D3OB00398AEI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.9
- Lukas Krep, Felix Schmalz, Florian Solbach, Leonid Komissarov, Thomas Nevolianis, Wassja A. Kopp, Toon Verstraelen, Kai Leonhard. A Reactive Molecular Dynamics Study of Chlorinated Organic Compounds. Part II: A ChemTraYzer Study of Chlorinated Dibenzofuran Formation and Decomposition Processes. ChemPhysChem 2023, 24
(7)
https://doi.org/10.1002/cphc.202200783EI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.3SWJTU A+
- Moritz Bensberg, Markus Reiher. Concentration‐Flux‐Steered Mechanism Exploration with an Organocatalysis Application. Israel Journal of Chemistry 2023, 8 https://doi.org/10.1002/ijch.202200123SCI升级版 化学4区SCI基础版 化学3区IF 2.3
- Jan P. Unsleber, Hongbin Liu, Leopold Talirz, Thomas Weymuth, Maximilian Mörchen, Adam Grofe, Dave Wecker, Christopher J. Stein, Ajay Panyala, Bo Peng, Karol Kowalski, Matthias Troyer, Markus Reiher. High-throughput
ab initio
reaction mechanism exploration in the cloud with automated multi-reference validation. The Journal of Chemical Physics 2023, 158
(8)
https://doi.org/10.1063/5.0136526EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.1SWJTU A++
- Yoshifumi Nishimura, Hiromi Nakai. Species-selective nanoreactor molecular dynamics simulations based on linear-scaling tight-binding quantum chemical calculations. The Journal of Chemical Physics 2023, 158
(5)
https://doi.org/10.1063/5.0132573EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.1SWJTU A++
- Choon Wee Kee. Molecular Understanding and Practical In Silico Catalyst Design in Computational Organocatalysis and Phase Transfer Catalysis—Challenges and Opportunities. Molecules 2023, 28
(4)
, 1715. https://doi.org/10.3390/molecules28041715SCI升级版 化学2区SCI基础版 化学3区IF 4.2SWJTU A+
- Pablo Ramos‐Sánchez, Jeremy N. Harvey, José A. Gámez. An automated method for graph‐based chemical space exploration and transition state finding. Journal of Computational Chemistry 2023, 44
(1)
, 27-42. https://doi.org/10.1002/jcc.27011EI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.4SWJTU A++
- Zhengkai Tu, Thijs Stuyver, Connor W. Coley. Predictive chemistry: machine learning for reaction deployment, reaction development, and reaction discovery. Chemical Science 2023, 14
(2)
, 226-244. https://doi.org/10.1039/D2SC05089G化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Yu Harabuchi, Hiroki Hayashi, Hideaki Takano, Tsuyoshi Mita, Satoshi Maeda. Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox‐Catalyzed Radical Reaction**. Angewandte Chemie International Edition 2023, 62
(1)
https://doi.org/10.1002/anie.202211936化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 16.1SWJTU A++
- Yu Harabuchi, Hiroki Hayashi, Hideaki Takano, Tsuyoshi Mita, Satoshi Maeda. Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox‐Catalyzed Radical Reaction**. Angewandte Chemie 2023, 135
(1)
https://doi.org/10.1002/ange.202211936
- Mingjian Wen, Evan Walter Clark Spotte-Smith, Samuel M. Blau, Matthew J. McDermott, Aditi S. Krishnapriyan, Kristin A. Persson. Chemical reaction networks and opportunities for machine learning. Nature Computational Science 2023, 3
(1)
, 12-24. https://doi.org/10.1038/s43588-022-00369-zEI检索IF 12.0
- Siyuan Gong, Yutong Wang, Yajie Tian, Li Wang, Guozhu Liu. Rapid enthalpy prediction of transition states using molecular graph convolutional network. AIChE Journal 2023, 69
(1)
https://doi.org/10.1002/aic.17269EI检索SCI升级版 工程技术3区SCI基础版 工程技术3区IF 3.5
- Rocío Durán, Nery Villegas-Escobar, Daniela E. Ortega, Ricardo A. Matute. The diabatic model of intermediate stabilization for reaction mechanism analysis: a link to valence bond and Marcus theories. 2023, 347-375. https://doi.org/10.1016/B978-0-32-390257-1.00018-8
- M. Podewitz. Towards predictive computational catalysis – a case study of olefin metathesis with Mo imido alkylidene N-heterocyclic carbene catalysts. 2022, 1-23. https://doi.org/10.1039/9781839169342-00001
- Cyrille Lavigne, Gabe Gomes, Robert Pollice, Alán Aspuru-Guzik. Guided discovery of chemical reaction pathways with imposed activation. Chemical Science 2022, 13
(46)
, 13857-13871. https://doi.org/10.1039/D2SC05135D化学TOPEI检索SCI升级版 化学1区SCI基础版 化学1区IF 7.6
- Tobias M. Pazdera, Johannes Wenz, Matthias Olzmann. The unimolecular decomposition of dimethoxymethane: channel switching as a function of temperature and pressure. Faraday Discussions 2022, 238 , 665-681. https://doi.org/10.1039/D2FD00039CEI检索SCI升级版 化学3区SCI基础版 化学3区IF 3.3
- Francesco Bosia, Thomas Weymuth, Markus Reiher. Ultra‐fast spectroscopy for
high‐throughput
and interactive quantum chemistry. International Journal of Quantum Chemistry 2022, 122
(19)
https://doi.org/10.1002/qua.26966EI检索SCI升级版 化学3区SCI基础版 化学4区IF 2.3
- Hiroki Hayashi, Hitomi Katsuyama, Hideaki Takano, Yu Harabuchi, Satoshi Maeda, Tsuyoshi Mita. In silico reaction screening with difluorocarbene for N-difluoroalkylative dearomatization of pyridines. Nature Synthesis 2022, 1
(10)
, 804-814. https://doi.org/10.1038/s44160-022-00128-y
- X. Liu, W. Wang, S. C. Wright, M. Doppelbauer, G. Meijer, S. Truppe, J. Pérez-Ríos. The chemistry of AlF and CaF production in buffer gas sources. The Journal of Chemical Physics 2022, 157
(7)
https://doi.org/10.1063/5.0098378EI检索SCI升级版 化学2区SCI基础版 化学3区IF 3.1SWJTU A++
- Kimichi Suzuki, Satoshi Maeda. Multistructural microiteration combined with QM/MM-ONIOM electrostatic embedding. Physical Chemistry Chemical Physics 2022, 24
(27)
, 16762-16773. https://doi.org/10.1039/D2CP02270BEI检索SCI升级版 化学3区SCI基础版 化学3区IF 2.9SWJTU A++
Learn about these metrics
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.
Recommended Articles
GFN2-xTB—An Accurate and Broadly Parametrized Self-Consistent Tight-Binding Quantum Chemical Method with Multipole Electrostatics and Density-Dependent Dispersion Contributions
Chemoton 2.0: Autonomous Exploration of Chemical Reaction Networks
Expansive Quantum Mechanical Exploration of Chemical Reaction Paths
Context-Driven Exploration of Complex Chemical Reaction Networks
Automated Transition State Search and Its Application to Diverse Types of Organic Reactions
Sponsored Content
Get an introduction to US patent law for scientists and engineers involved in business and tech.
Abstract
Figure 1
Figure 1. General strategies for the exploration of PESs. Left: local curvature information on the PES is exploited to identify TSs and products. Middle: through the application of heuristics new intermediates are identified. Right: intermediates and TSs are explored interactively. In the two latter cases of heuristics-based and interactive explorations, pathways need to be refined a posteriori to obtain MEPs. An efficient exploration protocol may combine strategies from different classes.
Figure 2
Figure 2. Schematic course of a typical quantum chemical calculation. (a) Traditionally, the most time-intensive step is the computation step on the CPU. (b) With increasing CPU power, the duration of quantum chemical calculations decreases for a fixed system size and some given electronic structure model. (c) For a quasi-instantaneous calculation, the most time-intensive step is now no longer the computation itself, but the bottleneck becomes the setup and the analysis of the results.
Figure 3
Figure 3. Main components of a real-time quantum chemistry framework. The central element is the molecular structure under study (center) that is displayed (top right) to the operator. The operator can move atoms and experience the effects of his manipulations with a computer mouse or a haptic device (top left). Single-point calculations run continuously in the background (bottom) and deliver the nuclear forces underlying the reactivity exploration as well as other relevant quantum chemical properties.
Figure 4
Figure 4. Combined strengths of three classes of exploration strategies result in a universally applicable exploration protocol.
References
This article references 262 other publications.
- 1Masters, C. Homogeneous Transition-Metal Catalysis: A Gentle Art, 1st ed.; Springer, 2011.There is no corresponding record for this reference.
- 2Vinu, R.; Broadbelt, L. J. Unraveling Reaction Pathways and Specifying Reaction Kinetics for Complex Systems. Annu. Rev. Chem. Biomol. Eng. 2012, 3, 29– 54, DOI: 10.1146/annurev-chembioeng-062011-0811082https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1GmtbnK&md5=c4ba8d6755e934d6a78993f8e67a6b85Unraveling reaction pathways and specifying reaction kinetics for complex systemsVinu, R.; Broadbelt, Linda J.Annual Review of Chemical and Biomolecular Engineering (2012), 3 (), 29-54CODEN: ARCBCY; ISSN:1947-5438. (Annual Reviews Inc.)A review. Many natural and industrial processes involve a complex set of competing reactions that include several different species. Detailed kinetic modeling of such systems can shed light on the important pathways involved in various transformations and therefore can be used to optimize the process conditions for the desired product compn. and properties. This review focuses on elucidating the various components involved in modeling the kinetics of pyrolysis and oxidn. of polymers. The elementary free radical steps that constitute the chain reaction mechanism of gas-phase/nonpolar liq.-phase processes are outlined. Specification of the rate coeffs. of the various reaction families, which is central to the theme of kinetics, is described. Construction of the reaction network on the basis of the types of end groups and reactive moieties in a polymer chain is discussed. Modeling frameworks based on the method of moments and kinetic Monte Carlo are evaluated using illustrations. Finally, the prospects and challenges in modeling biomass conversion are addressed.
- 3Ross, J. Determination of Complex Reaction Mechanisms. Analysis of Chemical, Biological and Genetic Networks. J. Phys. Chem. A 2008, 112, 2134– 2143, DOI: 10.1021/jp711313eThere is no corresponding record for this reference.
- 4Jorgensen, W. L. The Many Roles of Computation in Drug Discovery. Science 2004, 303, 1813– 1818, DOI: 10.1126/science.10963614https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXitFehu7w%253D&md5=77b2fac63e750ca7cdc7e4f35654549aThe Many Roles of Computation in Drug DiscoveryJorgensen, William L.Science (Washington, DC, United States) (2004), 303 (5665), 1813-1818CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. An overview is given on the diverse uses of computational chem. in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for detg. protein-ligand binding.
- 5Valdez, C. E.; Morgenstern, A.; Eberhart, M. E.; Alexandrova, A. N. Predictive Methods for Computational Metalloenzyme Redesign – a Test Case with Carboxypeptidase A. Phys. Chem. Chem. Phys. 2016, 18, 31744– 31756, DOI: 10.1039/C6CP02247B5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFCrsbbO&md5=b11bfcb0cc2fec4149ad6f9fc28ffa66Predictive methods for computational metalloenzyme redesign - a test case with carboxypeptidase AValdez, Crystal E.; Morgenstern, Amanda; Eberhart, Mark E.; Alexandrova, Anastassia N.Physical Chemistry Chemical Physics (2016), 18 (46), 31744-31756CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Computational metalloenzyme design is a multi-scale problem. It requires treating the metal coordination quantum mech., extensive sampling of the protein backbone, and addnl. accounting for the polarization of the active site by both the metal cation and the surrounding protein (a phenomenon called electrostatic preorganization). We bring together a combination of theor. methods that jointly offer these desired qualities: QM/DMD for mixed quantum-classical dynamic sampling, quantum theory of atoms in mols. (QTAIM) for the assessment of electrostatic preorganization, and D. Functional Theory (DFT) for mechanistic studies. Within this suite of principally different methods, there are both complementarity of capabilities and cross-validation. Using these methods, predictions can be made regarding the relative activities of related enzymes, as we show on the native Zn2+-dependent carboxypeptidase A (CPA), and its mutant proteins, which are hypothesized to hydrolyze modified substrates. For the native CPA, we replicated the catalytic mechanism and the rate in close agreement with the expt., giving validity to the QM/DMD predicted structure, the DFT mechanism, and the QTAIM assessment of catalytic activity. For most sequences of the modified substrate and tried CPA mutants, substantially worsened activity is predicted. However, for the substrate mutant that contains Asp instead of Phe at the C-terminus, one CPA mutant exhibits a reasonable activity, as predicted across the theor. methods. CPA is a well-studied system, and here it serves as a testing ground for the offered methods.
- 6Honkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Nørskov, J. K. Ammonia Synthesis from First-Principles Calculations. Science 2005, 307, 555– 5586https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslOjuw%253D%253D&md5=4c6066f84d200c9c587b6dd1dcd3b0bfAmmonia Synthesis from First-Principles CalculationsHonkala, K.; Hellman, A.; Remediakis, I. N.; Logadottir, A.; Carlsson, A.; Dahl, S.; Christensen, C. H.; Norskov, J. K.Science (Washington, DC, United States) (2005), 307 (5709), 555-558CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The rate of ammonia synthesis over a nanoparticle ruthenium catalyst can be calcd. directly on the basis of a quantum chem. treatment of the problem using d. functional theory. We compared the results to measured rates over a ruthenium catalyst supported on magnesium aluminum spinel. When the size distribution of ruthenium particles measured by transmission electron microscopy was used as the link between the catalyst material and the theor. treatment, the calcd. rate was within a factor of 3 to 20 of the exptl. rate. This offers hope for computer-based methods in the search for catalysts.
- 7Medford, A. J.; Wellendorff, J.; Vojvodic, A.; Studt, F.; Abild-Pedersen, F.; Jacobsen, K. W.; Bligaard, T.; Nørskov, J. K. Assessing the Reliability of Calculated Catalytic Ammonia Synthesis Rates. Science 2014, 345, 197– 200, DOI: 10.1126/science.12534867https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWjtLvK&md5=af3416666eeec422dd8f7c7543b9488eAssessing the reliability of calculated catalytic ammonia synthesis ratesMedford, Andrew J.; Wellendorff, Jess; Vojvodic, Aleksandra; Studt, Felix; Abild-Pedersen, Frank; Jacobsen, Karsten W.; Bligaard, Thomas; Norskov, Jens K.Science (Washington, DC, United States) (2014), 345 (6193), 197-200CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)We introduce a general method for estg. the uncertainty in calcd. materials properties based on d. functional theory calcns. We illustrate the approach for a calcn. of the catalytic rate of ammonia synthesis over a range of transition-metal catalysts. The correlation between errors in d. functional theory calcns. is shown to play an important role in reducing the predicted error on calcd. rates. Uncertainties depend strongly on reaction conditions and catalyst material, and the relative rates between different catalysts are considerably better described than the abs. rates. We introduce an approach for incorporating uncertainty when searching for improved catalysts by evaluating the probability that a given catalyst is better than a known std.
- 8Matera, S.; Maestri, M.; Cuoci, A.; Reuter, K. Predictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid Dynamics. ACS Catal. 2014, 4, 4081– 4092, DOI: 10.1021/cs501154e8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12kurjF&md5=e0f052a4546ccf857b9e898b8d08825bPredictive-Quality Surface Reaction Chemistry in Real Reactor Models: Integrating First-Principles Kinetic Monte Carlo Simulations into Computational Fluid DynamicsMatera, Sebastian; Maestri, Matteo; Cuoci, Alberto; Reuter, KarstenACS Catalysis (2014), 4 (11), 4081-4092CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)We present a numerical framework to integrate first-principles kinetic Monte Carlo (1p-kMC) based microkinetic models into the powerful computational fluid dynamics (CFD) package CatalyticFoam. This allows for the simultaneous account of a predictive-quality surface reaction kinetics inside an explicitly described catalytic reactor geometry. Crucial means toward an efficient and stable implementation are the exploitation of the disparate time scales of surface chem. and gas-phase transport, as well as the reliable interpolation of irregularly gridded 1p-kMC data by means of an error-based modified Shepard approach. We illustrate the capabilities of the framework using the CO oxidn. at Pd(100) and RuO2(110) model catalysts in different reactor configurations and fluid dynamic conditions as showcases. These showcases underscore both the necessity and value of having reliable treatments of the surface chem. and flow inside integrated multiscale catalysis simulations when aiming at an at.-scale understanding of the catalytic function in near-ambient environments. Our examples highlight how intricately this function is affected by specifics of the reactor geometry and heat dissipation channels on the one end, and on the other end by characteristics of the intrinsic catalytic activity that are only captured by treatments beyond prevalent mean-field rate equations.
- 9Reuter, K. Ab Initio Thermodynamics and First-Principles Microkinetics for Surface Catalysis. Catal. Lett. 2016, 146, 541– 563, DOI: 10.1007/s10562-015-1684-39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xps1CnsQ%253D%253D&md5=352bd644b8fabaf14fc7e70d0f29b5a0Ab Initio Thermodynamics and First-Principles Microkinetics for Surface CatalysisReuter, KarstenCatalysis Letters (2016), 146 (3), 541-563CODEN: CALEER; ISSN:1011-372X. (Springer)A review; ab initio thermodn. and first-principles microkinetic simulations have become std. tools in research on model catalysts. Complementing dedicated in situ expts. these techniques contribute to our evolving mechanistic understanding, in particular of a reaction-induced dynamical evolution of the working catalyst surface. This topical review surveys the methodol. foundations and ongoing developments of both techniques, and specifically illustrates the type of insights they provide in the context of in situ model catalyst studies. This insight points at substantial deviations from the std. picture that analyzes catalytic function merely in terms of properties of and processes at active sites as they emerge from a crystal lattice truncation of the nominal catalyst bulk material.
- 10Baxter, E. T.; Ha, M.-A.; Cass, A. C.; Alexandrova, A. N.; Anderson, S. L. Ethylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst Morphologies. ACS Catal. 2017, 7, 3322– 3335, DOI: 10.1021/acscatal.7b0040910https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVSqsbc%253D&md5=d1944c4c7de19d6e44ea69ac739c458dEthylene Dehydrogenation on Pt4,7,8 Clusters on Al2O3: Strong Cluster Size Dependence Linked to Preferred Catalyst MorphologiesBaxter, Eric T.; Ha, Mai-Anh; Cass, Ashley C.; Alexandrova, Anastassia N.; Anderson, Scott L.ACS Catalysis (2017), 7 (5), 3322-3335CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Catalytic dehydrogenation of ethylene on size-selected Ptn (n = 4, 7, 8) clusters deposited on the surface of Al2O3 was studied exptl. and theor. Clusters were mass-selected, deposited on the alumina support, and probed by a combination of low energy ion scattering, temp.-programmed desorption and reaction of C2D4 and D2, XPS, d. functional theory, and statistical mech. theory. Pt7 is identified as the most catalytically active cluster, while Pt4 and Pt8 exhibit comparable activities. The higher activity can be related to the cluster structure and particularly to the distribution of cluster morphologies accessible at the temps. and coverage with ethylene in catalytic conditions. Specifically, while Pt7 and Pt8 on alumina have very similar prismatic global min. geometries, Pt7 at higher temps. also has access to single-layer isomers, which become more and more predominant in the cluster catalyst ensemble upon increasing ethylene coverage. Single-layer isomers feature greater charge transfer from the support and more binding sites that activate ethylene for dehydrogenation rather than hydrogenation or desorption. Size-dependent susceptibility to coking and deactivation was also studied. Results show that size-dependent catalytic activity of clusters is not a simple property of single cluster geometry but the av. over a statistical ensemble at relevant conditions.
- 11Ha, M.-A.; Baxter, E. T.; Cass, A. C.; Anderson, S. L.; Alexandrova, A. N. Boron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3. J. Am. Chem. Soc. 2017, 139, 11568– 11575, DOI: 10.1021/jacs.7b0589411https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1GjsbrO&md5=c4fb4ca3671fed66af60f96ac51a86cbBoron Switch for Selectivity of Catalytic Dehydrogenation on Size-Selected Pt Clusters on Al2O3Ha, Mai-Anh; Baxter, Eric T.; Cass, Ashley C.; Anderson, Scott L.; Alexandrova, Anastassia N.Journal of the American Chemical Society (2017), 139 (33), 11568-11575CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Size-selected supported clusters of transition metals can be remarkable and highly tunable catalysts. A particular example is Pt clusters deposited on alumina, which have been shown to dehydrogenate hydrocarbons in a size-specific manner. Pt7, of the three sizes studied, is the most active and, therefore, like many other catalysts, deactivates by coking during reactions in hydrocarbon-rich environments. Using a combination of expt. and theory, we show that nanoalloying Pt7 with boron modifies the alkene-binding affinity to reduce coking. From a fundamental perspective, the comparison of exptl. and theor. results shows the importance of considering not simply the most stable cluster isomer, but rather the ensemble of accessible structures as it changes in response to temp. and reagent coverage.
- 12Ulissi, Z. W.; Medford, A. J.; Bligaard, T.; Nørskov, J. K. To Address Surface Reaction Network Complexity Using Scaling Relations Machine Learning and DFT Calculations. Nat. Commun. 2017, 8, 14621, DOI: 10.1038/ncomms1462112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czjtFamuw%253D%253D&md5=bde19b4dcb6abce90b2ea7ab073e1c6eTo address surface reaction network complexity using scaling relations machine learning and DFT calculationsUlissi Zachary W; Norskov Jens K; Medford Andrew J; Bligaard ThomasNature communications (2017), 8 (), 14621 ISSN:.Surface reaction networks involving hydrocarbons exhibit enormous complexity with thousands of species and reactions for all but the very simplest of chemistries. We present a framework for optimization under uncertainty for heterogeneous catalysis reaction networks using surrogate models that are trained on the fly. The surrogate model is constructed by teaching a Gaussian process adsorption energies based on group additivity fingerprints, combined with transition-state scaling relations and a simple classifier for determining the rate-limiting step. The surrogate model is iteratively used to predict the most important reaction step to be calculated explicitly with computationally demanding electronic structure theory. Applying these methods to the reaction of syngas on rhodium(111), we identify the most likely reaction mechanism. Propagating uncertainty throughout this process yields the likelihood that the final mechanism is complete given measurements on only a subset of the entire network and uncertainty in the underlying density functional theory calculations.
- 13Vereecken, L.; Glowacki, D. R.; Pilling, M. J. Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and Applications. Chem. Rev. 2015, 115, 4063– 4114, DOI: 10.1021/cr500488p13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmtVWqs7s%253D&md5=75c3bde1b210e3c1555d0c946f8e4976Theoretical Chemical Kinetics in Tropospheric Chemistry: Methodologies and ApplicationsVereecken, Luc; Glowacki, David R.; Pilling, Michael J.Chemical Reviews (Washington, DC, United States) (2015), 115 (10), 4063-4114CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review is presented. Chem. Kinetics in Tropospheric Chem. is studied.
- 14Ludlow, R. F.; Otto, S. Systems Chemistry. Chem. Soc. Rev. 2008, 37, 101– 108, DOI: 10.1039/B611921M14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVWhtQ%253D%253D&md5=151c83f30396538fccc0ea2f9c016d26Systems chemistryLudlow, R. Frederick; Otto, SijbrenChemical Society Reviews (2008), 37 (1), 101-108CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A tutorial review. The study of complex mixts. of interacting synthetic mols. has historically not received much attention from chemists, even though research into complexity is well established in the neighboring fields. However, with the huge recent interest in systems biol. and the availability of modern anal. techniques this situation is likely to change. In this tutorial review we discuss some of the incentives for developing systems chem. and we highlight the pioneering work in which mol. networks are making a splash. A distinction is made between networks under thermodn. and kinetic control. The former include dynamic combinatorial libraries while the latter involve pseudo-dynamic combinatorial libraries, oscillating reactions and networks of autocatalytic and replicating compds. These studies provide fundamental insights into the organizational principles of mol. networks and how these give rise to emergent properties such as amplification and feedback loops, and may eventually shed light on the origin of life. The knowledge obtained from the study of mol. networks should ultimately enable us to engineer new systems with properties and functions unlike any conventional materials.
- 15Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: Oxford, 2001.There is no corresponding record for this reference.
- 16Dewyer, A. L.; Argüelles, A. J.; Zimmerman, P. M. Methods for Exploring Reaction Space in Molecular Systems. WIREs Comput. Mol. Sci. 2018, 8, e1354 DOI: 10.1002/wcms.1354There is no corresponding record for this reference.
- 17Sameera, W. M. C.; Maeda, S.; Morokuma, K. Computational Catalysis Using the Artificial Force Induced Reaction Method. Acc. Chem. Res. 2016, 49, 763– 773, DOI: 10.1021/acs.accounts.6b0002317https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvFSnsb0%253D&md5=761857a94f5b7c7366b98650d8a42646Computational Catalysis Using the Artificial Force Induced Reaction MethodSameera, W. M. C.; Maeda, Satoshi; Morokuma, KeijiAccounts of Chemical Research (2016), 49 (4), 763-773CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)The artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy is an automatic approach to explore all important reaction paths of complex reactions. Most traditional methods in computational catalysis require guess reaction paths. On the other hand, the AFIR approach locates local min. (LMs) and transition states (TSs) of reaction paths without a guess, and therefore finds unanticipated as well as anticipated reaction paths. The AFIR method has been applied for multicomponent org. reactions, such as the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer catalysis. In the presence of several reactants, many equil. structures are possible, leading to a no. of reaction pathways. The AFIR method in the GRRM strategy dets. all of the important equil. structures and subsequent reaction paths systematically. As the AFIR search is fully automatic, exhaustive trial-and-error and guess-and-check processes by the user can be eliminated. At the same time, the AFIR search is systematic, and therefore a more accurate and comprehensive description of the reaction mechanism can be detd.The AFIR method has been used for the study of full catalytic cycles and reaction steps in transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron-catalyzed carbon-carbon bond formation reactions in aq. media. Some AFIR applications have targeted the selectivity-detg. step of transition-metal-catalyzed asym. reactions, including stereoselective water-tolerant lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of establishing the selectivity of a reaction, systematic sampling of the transition states is crit. In this direction, AFIR is very useful for performing a systematic and automatic detn. of TSs. In the presence of a comprehensive description of the transition states, the selectivity of the reaction can be calcd. more accurately.For relatively large mol. systems, the computational cost of AFIR searches can be reduced by using the ONIOM(QM:QM) or ONIOM(QM:MM) methods. In common practice, d. functional theory (DFT) with a relatively small basis set is used for the high-level calcn., while a semiempirical approach or a force field description is used for the low-level calcn. After approx. LMs and TSs are detd., std. computational methods (e.g., DFT with a large basis set) are used for the full mol. system to det. the true LMs and TSs and to rationalize the reaction mechanism and selectivity of the catalytic reaction.The examples in this Account evidence that the AFIR method is a powerful approach for accurate prediction of the reaction mechanisms and selectivities of complex catalytic reactions. Therefore, the AFIR approach in the GRRM strategy is very useful for computational catalysis.
- 18Hawkins, P. C. D. Conformation Generation: The State of the Art. J. Chem. Inf. Model. 2017, 57, 1747– 1756, DOI: 10.1021/acs.jcim.7b0022118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFagu7bE&md5=776818e66798d1987e015440a28e208eConformation Generation: The State of the ArtHawkins, Paul C. D.Journal of Chemical Information and Modeling (2017), 57 (8), 1747-1756CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The generation of conformations for small mols. is a problem of continuing interest in cheminformatics and computational drug discovery. This review will present an overview of methods used to sample conformational space, focusing on those methods designed for org. mols. commonly of interest in drug discovery. Different approaches to both the sampling of conformational space and the scoring of conformational stability will be compared and contrasted, with an emphasis on those methods suitable for conformer sampling of large nos. of drug-like mols. Particular attention will be devoted to the appropriate utilization of information from exptl. solid-state structures in validating and evaluating the performance of these tools. The review will conclude with some areas worthy of further investigation.
- 19Ohno, K.; Maeda, S. A Scaled Hypersphere Search Method for the Topography of Reaction Pathways on the Potential Energy Surface. Chem. Phys. Lett. 2004, 384, 277– 282, DOI: 10.1016/j.cplett.2003.12.03019https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXksFWguw%253D%253D&md5=d695800fcf7c758ae9e5f6213d187edaA scaled hypersphere search method for the topography of reaction pathways on the potential energy surfaceOhno, Koichi; Maeda, SatoshiChemical Physics Letters (2004), 384 (4-6), 277-282CODEN: CHPLBC; ISSN:0009-2614. (Elsevier Science B.V.)An algorithm for finding pathways to transition states (TS) or dissocn. channels (DC) from equil. structures (EQ) on the potential energy surface (PES) is presented. The pathways around an EQ can be discovered at min. on the scaled hypersphere which would have a const. energy when the potentials are harmonic. Topog. maps including all TS, DC, and EQ were obtained for ab initio PES of H2O and HCHO in the MP2/3-21G level. The present scaled hypersphere search technique in combination with a downhill-walk algorithm enables us to make a topog. anal. of the PES for a given chem. compn.
- 20Maeda, S.; Ohno, K. Ab Initio Studies on Synthetic Routes of Glycine from Simple Molecules via Ammonolysis of Acetolactone: Applications of the Scaled Hypersphere Search Method. Chem. Lett. 2004, 33, 1372– 1373, DOI: 10.1246/cl.2004.1372There is no corresponding record for this reference.
- 21Maeda, S.; Ohno, K. Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to Ab Initio Surfaces of Formaldehyde and Propyne Molecules. J. Phys. Chem. A 2005, 109, 5742– 5753, DOI: 10.1021/jp051316221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksl2mtLk%253D&md5=68d94d344ec0774f5313ba93e456ffe3Global Mapping of Equilibrium and Transition Structures on Potential Energy Surfaces by the Scaled Hypersphere Search Method: Applications to ab Initio Surfaces of Formaldehyde and Propyne MoleculesMaeda, Satoshi; Ohno, KoichiJournal of Physical Chemistry A (2005), 109 (25), 5742-5753CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Tech. details of a new global mapping technique for finding equil. (EQ) and transition structures (TS) on potential energy surfaces (PES), the scaled hypersphere search (SHS) method (Ohno, K.; Maeda, S. Chem. Phys. Lett. 2004, 384, 277), are presented. On the basis of a simple principle that reaction pathways are found as anharmonic downward distortions of PES around an EQ point, the reaction pathways can be obtained as energy min. on the scaled hypersphere surface, which would have a const. energy when the potentials are harmonic. Connections of SHS paths between each EQ are very similar to corresponding intrinsic reaction coordinate (IRC) connections. The energy max. along the SHS path reaches a region in close proximity to the TS of the reaction pathway, and the subsequent geometry optimization from the SHS max. structure easily converges to the TS. The SHS method, using the one-after-another algorithm connecting EQ and TS, considerably reduces the multidimensional space to be searched to certain limited regions around the pathways connecting each EQ with the neighboring TS. Applications of the SHS method have been made to ab initio surfaces of formaldehyde and propyne mols. to obtain systematically five EQ and nine TS for formaldehyde and seven EQ and 32 TS for propyne.
- 22Ohno, K.; Maeda, S. Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted Analogues. J. Phys. Chem. A 2006, 110, 8933– 8941, DOI: 10.1021/jp061149l22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlvVWlsLk%253D&md5=b057c5984bdd877c2a57f80cfe6aa8a6Global Reaction Route Mapping on Potential Energy Surfaces of Formaldehyde, Formic Acid, and Their Metal-Substituted AnaloguesOhno, Koichi; Maeda, SatoshiJournal of Physical Chemistry A (2006), 110 (28), 8933-8941CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Global reaction route mapping of equil. structures, transition structures, and their connections on potential energy surface (PES) has been done for MCHO (M = H, Li, Na, Al, Cu) and HCO2M (M = H, Li). A one-after-another technique based on the scaled hypersphere search method has been successfully applied to exploring unknown chem. structures, transition structures, and reaction pathways for organometallic systems. Upon metal substitution, considerable changes of stable structures, reaction pathways, and relative heights of transition structures have been discovered, though some features are similar among the analogs. Al and Cu atoms were found to behave as very strong scissors to cut the CO double bond in MCHO. Energy profiles of the CO insertion into Li-H and Li-CH3 bonds were found to be very similar, esp. around the structures where the Li atom is not directly connected with the Me group, which indicates little effects of alkyl substitution on the reaction route topol.
- 23Maeda, S.; Ohno, K.; Morokuma, K. Systematic Exploration of the Mechanism of Chemical Reactions: The Global Reaction Route Mapping (GRRM) Strategy Using the ADDF and AFIR Methods. Phys. Chem. Chem. Phys. 2013, 15, 3683– 3701, DOI: 10.1039/c3cp44063j23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXislynsrg%253D&md5=3091bebd5edabab18bdabe51eb001e65Systematic exploration of the mechanism of chemical reactions: the global reaction route mapping (GRRM) strategy using the ADDF and AFIR methodsMaeda, Satoshi; Ohno, Koichi; Morokuma, KeijiPhysical Chemistry Chemical Physics (2013), 15 (11), 3683-3701CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Global reaction route mapping (GRRM), a fully-automated search for all important reaction pathways relevant to a given purpose, from quantum chem. calcns. enables systematic elucidation of complex chem. reaction mechanisms. However, GRRM had previously been limited to very simple systems. This is mainly because such calcns. are highly demanding even in small systems when a brute-force sampling is considered. Hence, the authors have developed two independent but complementary methods: anharmonic downward distortion following (ADDF) and artificial force induced reaction (AFIR) methods. ADDF can follow reaction pathways starting from local min. on the potential energy surface (PES) toward transition structures (TSs) and dissocn. channels. AFIR can find pathways starting from two or more reactants toward TSs for their associative reactions. ADDF searches for A X type isomerization and A X + Y type dissocn. pathways, whereas AFIR finds A + B X (+ Y) type associative pathways. Both follow special paths called the ADDF path and the AFIR path, and these tend to pass through near TSs of corresponding reaction pathways, giving approx. TSs. Such approx. TSs can easily be reoptimized to corresponding true TSs by std. geometry optimizations. From these two methods, the authors proposed practical strategies of GRRM. The GRRM strategies were applied to a variety of chem. systems ranging from thermal- and photochem.-reactions in small systems to organometallic- and enzyme-catalysis, from quantum chem. calcns. In this perspective, the authors present an overview of the GRRM strategies and some results of applications. Their practical usage for systematic prediction is also discussed.
- 24Satoh, H.; Oda, T.; Nakakoji, K.; Uno, T.; Tanaka, H.; Iwata, S.; Ohno, K. Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers. J. Chem. Theory Comput. 2016, 12, 5293– 5308, DOI: 10.1021/acs.jctc.6b0043924https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFOktr%252FF&md5=a395292cdbf67ed58b06748344d48939Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of D-Glucose ConformersSatoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, KoichiJournal of Chemical Theory and Computation (2016), 12 (11), 5293-5308CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)This paper describes approach that is built upon the potential energy surface (PES)-based conformational anal. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search was achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the min. and TS structures by simply taking into account the math. feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equil. (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalcn. anal. of the deduced r-map is interactively carried out using the RMapViewer software the authors have developed. This paper presents computational details of the PES-based conformational anal. and its application to D-glucose. The calcns. were performed for an isolated glucose mol. in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-D-glucose is composed of 201 Equiv and 435 TS conformers and that for β-D-glucose is composed of 202 Equiv and 371 TS conformers. For the postcalcn. anal. of the conformational r-maps by using the RMapViewer software program the authors found multiple min. energy paths (MEPs) between global min. of 1C4 and 4C1 chair conformations. The anal. using RMapViewer allows us to confirm the thermodn. and kinetic predominance of 4C1 conformations; i.e., the potential energy of the global min. of 4C1 is lower than that of 1C4 (thermodn. predominance) and that the highest energy of those of all the TS structures along a route from 4C1 to 1C4 is lower than that of 1C4 to 4C1 (kinetic predominance).
- 25Maeda, S.; Morokuma, K. A Systematic Method for Locating Transition Structures of A+B→X Type Reactions. J. Chem. Phys. 2010, 132, 241102, DOI: 10.1063/1.345790325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvFShtLs%253D&md5=9260f723c31e0b78b5677bb4a89f21d7Communications: A systematic method for locating transition structures of A + B → X type reactionsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Physics (2010), 132 (24), 241102/1-241102/4CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Search for transition structures (TSs) as first-order saddles is one of the most important tasks in theor. study of chem. reaction. Although automated search has been established either by starting from a local min. (MIN) or by connecting two MINs, there is no systematic method which can locate TSs of A + B → X (+ Y) type reactions starting from sepd. reactants. We propose such an approach for the first time; it was demonstrated to work very well in the SN2, Diels-Alder, and Wittig reactions. (c) 2010 American Institute of Physics.
- 26Maeda, S.; Morokuma, K. Finding Reaction Pathways of Type A+B→X: Toward Systematic Prediction of Reaction Mechanisms. J. Chem. Theory Comput. 2011, 7, 2335– 2345, DOI: 10.1021/ct200290m26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXosVCktro%253D&md5=85e666d25ec4858a5150bae96893f52aFinding Reaction Pathways of Type A + B → X: Toward Systematic Prediction of Reaction MechanismsMaeda, Satoshi; Morokuma, KeijiJournal of Chemical Theory and Computation (2011), 7 (8), 2335-2345CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In these five decades, many useful tools have been developed for exploring quantum chem. potential energy surfaces. The success in theor. studies of chem. reaction mechanisms has been greatly supported by these tools. However, systematic prediction of reaction mechanisms starting only from given reactants and catalysts is still very difficult. Toward this goal, we describe the artificial force induced reaction (AFIR) method for automatically finding reaction paths of type A + B → X (+ Y). By imposing an artificial force to given reactants and catalysts, the method can find the reactive sites very efficiently. Further pressing by the artificial force provides approx. transition states and product structures, which can be easily reoptimized to the corresponding true ones. This procedure can be executed very efficiently just by minimizing a single function called the AFIR function. All important reaction paths can be found by repeating this cycle starting from many initial orientations. We also discuss perspectives of automated reaction path search methods toward the above goal.
- 27Maeda, S.; Taketsugu, T.; Morokuma, K. Exploring Transition State Structures for Intramolecular Pathways by the Artificial Force Induced Reaction Method. J. Comput. Chem. 2014, 35, 166– 173, DOI: 10.1002/jcc.2348127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaqs77J&md5=18ee5becec9b21d0bdcef4d37b50a48dExploring transition state structures for intramolecular pathways by the artificial force induced reaction methodMaeda, Satoshi; Taketsugu, Tetsuya; Morokuma, KeijiJournal of Computational Chemistry (2014), 35 (2), 166-173CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Finding all required transition state (TS) structures is an important but hard task in theor. study of complex reaction mechanisms. An efficient automated TS search method, artificial force induced reaction (AFIR), was extended to intramol. reactions. The AFIR method was developed for intermol. associative pathways between two or more reactants. Although it also was applied to intramol. reactions by dividing mols. manually into fragments, the fragmentation scheme was not automated. The authors propose an automated fragmentation scheme. Using this fragmentation scheme and the AFIR method, a fully automated search algorithm for intramol. pathways is introduced. This version for intramol. reactions is called single-component AFIR (SC-AFIR), to distinguish it from multicomponent AFIR for intermol. reactions. SC-AFIR was tested with two reactions, the Claisen rearrangement and the first step of cobalt-catalyzed hydroformylation, and successfully located all important pathways reported in the literature. © 2013 Wiley Periodicals, Inc.
- 28Maeda, S.; Harabuchi, Y.; Takagi, M.; Taketsugu, T.; Morokuma, K. Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces. Chem. Rec. 2016, 16, 2232– 2248, DOI: 10.1002/tcr.20160004328https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XptV2iurg%253D&md5=fb8514d68f9fefc53f4d5f9ad8e19e06Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy SurfacesMaeda, Satoshi; Harabuchi, Yu; Takagi, Makito; Taketsugu, Tetsuya; Morokuma, KeijiChemical Record (2016), 16 (5), 2232-2248CODEN: CRHEAK; ISSN:1528-0691. (Wiley-VCH Verlag GmbH & Co. KGaA)In this account, a tech. overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chem. reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimol. and multicomponent reactions and the latter to unimol. isomerization and dissocn. reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene mol. Finally, possible applications of the AFIR method are discussed.
- 29Yoshimura, T.; Maeda, S.; Taketsugu, T.; Sawamura, M.; Morokuma, K.; Mori, S. Exploring the Full Catalytic Cycle of Rhodium(I)–BINAP-Catalysed Isomerisation of Allylic Amines: A Graph Theory Approach for Path Optimisation. Chem. Sci. 2017, 8, 4475– 4488, DOI: 10.1039/C7SC00401J29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntlWgt7s%253D&md5=c2ab51df0053f782bc9e9f5323ec2358Exploring the full catalytic cycle of rhodium(I)-BINAP-catalysed isomerisation of allylic amines: a graph theory approach for path optimisationYoshimura, Takayoshi; Maeda, Satoshi; Taketsugu, Tetsuya; Sawamura, Masaya; Morokuma, Keiji; Mori, SeijiChemical Science (2017), 8 (6), 4475-4488CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)We explored the reaction mechanism of the cationic rhodium(I)-BINAP complex catalyzed isomerization of allylic amines using the artificial force induced reaction method with the global reaction route mapping strategy, which enabled us to search for various reaction paths without assumption of transition states. The entire reaction network was reproduced in the form of a graph, and reasonable paths were selected from the complicated network using Prim's algorithm. As a result, a new dissociative reaction mechanism was proposed. Our comprehensive reaction path search provided rationales for the E/Z and S/R selectivities of the stereoselective reaction.
- 30Puripat, M.; Ramozzi, R.; Hatanaka, M.; Parasuk, W.; Parasuk, V.; Morokuma, K. The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction. J. Org. Chem. 2015, 80, 6959– 6967, DOI: 10.1021/acs.joc.5b0040730https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVans7nM&md5=7f6185df4c8e5c3802f013bc36a694c7The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent ReactionPuripat, Maneeporn; Ramozzi, Romain; Hatanaka, Miho; Parasuk, Waraporn; Parasuk, Vudhichai; Morokuma, KeijiJournal of Organic Chemistry (2015), 80 (14), 6959-6967CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The recently developed artificial force induced reaction (AFIR) method was applied to search systematically all possible multicomponent pathways for the Biginelli reaction mechanism. The most favorable pathway starts with the condensation of the urea and benzaldehyde, followed by the addn. of Et acetoacetate. Remarkably, a second urea mol. catalyzes nearly every step of the reaction. Thus, the Biginelli reaction is a urea-catalyzed multicomponent reaction. The reaction mechanism was found to be identical in both protic and aprotic solvents.
- 31Saitta, A. M.; Saija, F. Miller Experiments in Atomistic Computer Simulations. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 13768– 13773, DOI: 10.1073/pnas.140289411131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSju7nN&md5=711514af5c0a3a8d6d0a226d29be2d8bMiller experiments in atomistic computer simulationsSaitta, Antonino Marco; Saija, FranzProceedings of the National Academy of Sciences of the United States of America (2014), 111 (38), 13768-13773CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The celebrated Miller expts. reported on the spontaneous formation of amino acids from a mixt. of simple mols. reacting under an elec. discharge, giving birth to the research field of prebiotic chem. However, the chem. reactions involved in those expts. have never been studied at the at. level. Here the authors report on, to the authors' knowledge, the first ab initio computer simulations of Miller-like expts. in the condensed phase. The authors' study, based on the recent method of treatment of aq. systems under elec. fields and on metadynamics anal. of chem. reactions, shows that glycine spontaneously forms from mixts. of simple mols. once an elec. field is switched on and identifies formic acid and formamide as key intermediate products of the early steps of the Miller reactions, and the crucible of formation of complex biol. mols.
- 32Wang, L.-P.; Titov, A.; McGibbon, R.; Liu, F.; Pande, V. S.; Martínez, T. J. Discovering Chemistry with an Ab Initio Nanoreactor. Nat. Chem. 2014, 6, 1044– 1048, DOI: 10.1038/nchem.209932https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVGitbnI&md5=201fe998c04f0c9b9a7aa6ebf329a2c5Discovering chemistry with an ab initio nanoreactorWang, Lee-Ping; Titov, Alexey; McGibbon, Robert; Liu, Fang; Pande, Vijay S.; Martinez, Todd J.Nature Chemistry (2014), 6 (12), 1044-1048CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)Chem. understanding is driven by the exptl. discovery of new compds. and reactivity, and is supported by theory and computation that provide detailed phys. insight. Although theor. and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodol. and computational advances harken the advent of their principal role in discovery. Here, we report the development and application of the ab initio nanoreactor-a highly accelerated first-principles mol. dynamics simulation of chem. reactions that discovers new mols. and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor, we show new pathways for glycine synthesis from primitive compds. proposed to exist on the early Earth, which provide new insight into the classic Urey-Miller expt. These results highlight the emergence of theor. and computational chem. as a tool for discovery, in addn. to its traditional role of interpreting exptl. findings.
- 33Wang, L.-P.; McGibbon, R. T.; Pande, V. S.; Martinez, T. J. Automated Discovery and Refinement of Reactive Molecular Dynamics Pathways. J. Chem. Theory Comput. 2016, 12, 638– 649, DOI: 10.1021/acs.jctc.5b0083033https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVGku7nL&md5=6a731baa0767e0105247b156289fe8baAutomated Discovery and Refinement of Reactive Molecular Dynamics PathwaysWang, Lee-Ping; McGibbon, Robert T.; Pande, Vijay S.; Martinez, Todd J.Journal of Chemical Theory and Computation (2016), 12 (2), 638-649CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe a flexible and broadly applicable energy refinement method, "nebterpolation," for identifying and characterizing the reaction events in a mol. dynamics (MD) simulation. The new method is applicable to ab initio simulations with hundreds of atoms contg. complex and multimol. reaction events. A key aspect of nebterpolation is smoothing of the reactive MD trajectory in internal coordinates to initiate the search for the reaction path on the potential energy surface. We apply nebterpolation to analyze the reaction events in an ab initio nanoreactor simulation that discovers new mols. and mechanisms, including a C-C coupling pathway for glycolaldehyde synthesis. We find that the new method, which incorporates information from the MD trajectory that connects reactants with products, produces a dramatically distinct set of min. energy paths compared to existing approaches that start from information for the reaction end points alone. The energy refinement method described here represents a key component of an emerging simulation paradigm where mol. dynamics simulations are applied to discover the possible reaction mechanisms.
- 34Meuwly, M. Reactive Molecular Dynamics: From Small Molecules to Proteins. WIREs Comput. Mol. Sci. 2018, 0, e1386 DOI: 10.1002/wcms.1386There is no corresponding record for this reference.
- 35van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A 2001, 105, 9396– 9409, DOI: 10.1021/jp004368u35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFChu78%253D&md5=ea59efc08d5e135745df988f2006a7fdReaxFF: A Reactive Force Field for Hydrocarbonsvan Duin, Adri C. T.; Dasgupta, Siddharth; Lorant, Francois; Goddard, William A., IIIJournal of Physical Chemistry A (2001), 105 (41), 9396-9409CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)To make practical the mol. dynamics simulation of large scale reactive chem. systems (1000 s of atoms), the authors developed ReaxFF, a force field for reactive systems. ReaxFF uses a general relation between bond distance and bond order on one hand and between bond order and bond energy however, that leads to proper dissocn. of bonds to sepd. atoms. Other valence terms present in the force field (angle and torsion) are defined in terms of the same bond orders so that all these terms go to zero smoothly as bonds break. In addn., ReaxFF has Coulomb and Morse (van der Waals) potentials to describe nonbond interactions between all atoms (no exclusions). These nonbond interactions are shielded at short range so that the Coulomb and van der Waals interactions become const. as Rij → 0. The authors report here the ReaxFF for hydrocarbons. The parameters were derived from quantum chem. calcns. on bond dissocn. and reactions of small mols. plus heat of formation and geometry data for a no. of stable hydrocarbon compds. The ReaxFF provides a good description of these data. Generally, the results are of an accuracy similar or better than PM3, while ReaxFF is ∼100 times faster. In turn, the PM3 is ∼100 times faster than the QC calcns. Thus, with ReaxFF the authors hope to be able to study complex reactions in hydrocarbons.
- 36Döntgen, M.; Przybylski-Freund, M.-D.; Kröger, L. C.; Kopp, W. A.; Ismail, A. E.; Leonhard, K. Automated Discovery of Reaction Pathways, Rate Constants, and Transition States Using Reactive Molecular Dynamics Simulations. J. Chem. Theory Comput. 2015, 11, 2517– 2524, DOI: 10.1021/acs.jctc.5b0020136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vjt1Gjtg%253D%253D&md5=7f936903e2258f886ccce3fc8fef0996Automated discovery of reaction pathways, rate constants, and transition states using reactive molecular dynamics simulationsDontgen Malte; Przybylski-Freund Marie-Dominique; Kroger Leif C; Kopp Wassja A; Ismail Ahmed E; Leonhard KaiJournal of chemical theory and computation (2015), 11 (6), 2517-24 ISSN:.We provide a methodology for deducing quantitative reaction models from reactive molecular dynamics simulations by identifying, quantifying, and evaluating elementary reactions of classical trajectories. Simulations of the inception stage of methane oxidation are used to demonstrate our methodology. The agreement of pathways and rates with available literature data reveals the potential of reactive molecular dynamics studies for developing quantitative reaction models.
- 37Fischer, S.; Karplus, M. Conjugate Peak Refinement: An Algorithm for Finding Reaction Paths and Accurate Transition States in Systems with Many Degrees of Freedom. Chem. Phys. Lett. 1992, 194, 252– 261, DOI: 10.1016/0009-2614(92)85543-J37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XltFSqtrk%253D&md5=938aae7d35f6942adbd76bf19c19cf9dConjugate peak refinement: an algorithm for finding reaction paths and accurate transition states in systems with many degrees of freedomFischer, Stefan; Karplus, MartinChemical Physics Letters (1992), 194 (3), 252-61CODEN: CHPLBC; ISSN:0009-2614.An algorithm is presented for detg. multidimensional reaction coordinates between two known conformers. Only the energy function and its gradient are required. The resulting paths follow the adiabatic energy valleys and have energy max. that are true saddle points, which can be multiple along each path. The method is suitable for the study of complex isomerization reactions, including allosteric transitions in proteins and more general conformational changes of macromols.
- 38Florián, J.; Goodman, M. F.; Warshel, A. Computer Simulation of the Chemical Catalysis of DNA Polymerases: Discriminating between Alternative Nucleotide Insertion Mechanisms for T7 DNA Polymerase. J. Am. Chem. Soc. 2003, 125, 8163– 8177, DOI: 10.1021/ja028997o38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXksFWgsbY%253D&md5=98029baf5458f072872a0746ea5ab990Computer simulation of the chemical catalysis of DNA polymerases: Discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymeraseFlorian, Jan; Goodman, Myron F.; Warshel, AriehJournal of the American Chemical Society (2003), 125 (27), 8163-8177CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Understanding the chem. step in the catalytic reaction of DNA polymerases is essential for elucidating the mol. basis of the fidelity of DNA replication. The present work evaluates the free energy surface for the nucleotide transfer reaction of T7 polymerase by free energy perturbation/empirical valence bond (FEP/EVB) calcns. A key aspect of the enzyme simulation is a comparison of enzymic free energy profiles with the corresponding ref. reactions in water using the same computational methodol., thereby enabling a quant. est. for the free energy of the nucleotide insertion reaction. The reaction is driven by the FEP/EVB methodol. between valence bond structures representing the reactant, pentacovalent intermediate, and the product states. This pathway corresponds to three microscopic chem. steps, deprotonation of the attacking group, a nucleophilic attack on the Pα atom of the dNTP substrate, and departure of the leaving group. Three different mechanisms for the first microscopic step, the generation of the RO- nucleophile from the 3'-OH hydroxyl of the primer, are examd.: (i) proton transfer to the bulk solvent, (ii) proton transfer to one of the ionic oxygens of the Pα phosphate group, and (iii) proton transfer to the ionized Asp 654 residue. The most favorable reaction mechanism in T7 pol is predicted to involve the proton transfer to Asp 654. This finding sheds light on the long standing issue of the actual role of conserved aspartates. The structural preorganization that helps to catalyze the reaction is also considered and analyzed. The overall calcd. mechanism consists of three subsequent steps with a similar activation free energy of about 12 kcal/mol. The similarity of the activation barriers of the three microscopic chem. steps indicates that the T7 polymerase may select against the incorrect dNTP substrate by raising any of these barriers. The relative height of these barriers comparing right and wrong dNTP substrates should therefore be a primary focus of future computational studies of the fidelity of DNA polymerases.
- 39Garcia-Viloca, M.; Gao, J.; Karplus, M.; Truhlar, D. G. How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. Science 2004, 303, 186– 195, DOI: 10.1126/science.108817239https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtlGhug%253D%253D&md5=35766752530af526c8bdc99774a8e9daHow enzymes work: Analysis by modern rate theory and computer simulationsGarcia-Viloca, Mireia; Gao, Jiali; Karplus, Martin; Truhlar, Donald G.Science (Washington, DC, United States) (2004), 303 (5655), 186-195CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review and discussion. Advances in transition state theory and computer simulations are providing new insights into the sources of enzyme catalysis. Both the lowering of the activation free energy and changes in the generalized transmission coeff. (recrossing of the transition state, tunneling, and nonequil. contributions) can play a role. A framework for understanding these effects is presented, and the contributions of the different factors, as illustrated by specific enzymes, are identified and quantified by computer simulations. The resulting understanding of enzyme catalysis is used to comment on alternative proposals of how enzymes work.
- 40Imhof, P.; Fischer, S.; Smith, J. C. Catalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical Analysis. Biochemistry 2009, 48, 9061– 9075, DOI: 10.1021/bi900585m40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtV2mtbvP&md5=88ce54a5f9131bc8ad11b1dbd07f8e6eCatalytic Mechanism of DNA Backbone Cleavage by the Restriction Enzyme EcoRV: A Quantum Mechanical/Molecular Mechanical AnalysisImhof, Petra; Fischer, Stefan; Smith, Jeremy C.Biochemistry (2009), 48 (38), 9061-9075CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)Endonucleases, such as the restriction enzyme EcoRV, cleave the DNA backbone at a specific recognition sequence. We have investigated the catalytic mechanism of backbone phosphodiester hydrolysis by the restriction enzyme EcoRV by means of hybrid quantum mech./mol. mech. calcns. An exhaustive computation of different reaction pathways is performed, thus generating a network of pathways. Comparison of the computed (AM1d/MM) enzymic reaction pathways with an analogous mechanism for small-mol. model systems [AM1/d and B3LYP/6-31++G(d,p)] reveals that the transition barriers for associative hydrolysis, which is more probable in the model systems, are not lowered by the enzyme. Instead, a reaction mechanism which has mostly dissociative character is more likely. The protein environment is tuned to significantly electrostatically stabilize the transition state structures. The direct catalytic impact of essential residues is detd. The magnesium metal ion activates a water mol., thus facilitating protonation of the leaving group. A redn. of the coordination no. of the magnesium metal ion from six to four upon the positioning of the attacking water mol. explains why larger metal ions, such as calcium, are not catalytically active. The nucleophile is generated by the transfer of a proton from the attacking water mol. to a carboxylic oxygen atom of aspartate 90. The catalytic effect of lysine 92 involves proper positioning of the scissile phosphate group and, more importantly, stabilization of the metaphosphate intermediate in an orientation optimal for attack of the nucleophile.
- 41Reidelbach, M.; Betz, F.; Mäusle, R. M.; Imhof, P. Proton Transfer Pathways in an Aspartate-Water Cluster Sampled by a Network of Discrete States. Chem. Phys. Lett. 2016, 659, 169– 175, DOI: 10.1016/j.cplett.2016.07.021There is no corresponding record for this reference.
- 42Imhof, P. A. Networks Approach to Modeling Enzymatic Reactions. Methods Enzymol. 2016, 578, 249– 271, DOI: 10.1016/bs.mie.2016.05.025There is no corresponding record for this reference.
- 43Senn, H. M.; Thiel, W. QM/MM Methods for Biological Systems. Top. Curr. Chem. 2007, 268, 173– 290, DOI: 10.1007/128_2006_08443https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvVOlt7c%253D&md5=bf5f07823db75b3e05018ed47b70d2c1QM/MM methods for biological systemsSenn, Hans Martin; Thiel, WalterTopics in Current Chemistry (2007), 268 (Atomistic Approaches in Modern Biology), 173-290CODEN: TPCCAQ; ISSN:0340-1022. (Springer GmbH)A review. Thirty years after the seminal contribution by Warshel and Levitt, we review the state of the art of combined quantum-mechanics/mol.-mechanics (QM/MM) methods, with a focus on biomol. systems. We provide a detailed overview of the methodol. of QM/MM calcns. and their use within optimization and simulation schemes. A tabular survey of recent applications, mostly to enzymic reactions, is given.
- 44Senn, H. M.; Thiel, W. QM/MM Studies of Enzymes. Curr. Opin. Chem. Biol. 2007, 11, 182– 187, DOI: 10.1016/j.cbpa.2007.01.68444https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjvFegurw%253D&md5=361cc5b164e23e5a71dac6f4bbf7d673QM/MM studies of enzymesSenn, Hans Martin; Thiel, WalterCurrent Opinion in Chemical Biology (2007), 11 (2), 182-187CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) methods are making rapid progress both methodol. and with respect to their range of application. Mechanistic studies on enzymes, including contributions toward the understanding of enzyme catalysis, continue to be a major target. They are joined by calcns. of pKa values, redox properties, ground- and excited-state spectroscopic parameters, and excited-state dynamics. Methodol. advances include improved QM/MM schemes, in particular new approaches for an effective treatment of the QM-MM electrostatic interactions, and the incorporation of new efficient and accurate QM methods in QM/MM schemes.
- 45Senn, H. M.; Thiel, W. QM/MM Methods for Biomolecular Systems. Angew. Chem., Int. Ed. 2009, 48, 1198– 1229, DOI: 10.1002/anie.20080201945https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXitFOqs7g%253D&md5=c51da58b0525651c71f9c393a79023beQM/MM methods for biomolecular systemsSenn, Hans Martin; Thiel, WalterAngewandte Chemie, International Edition (2009), 48 (7), 1198-1229CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Combined quantum-mechanics/mol.-mechanics (QM/MM) approaches have become the method of choice for modeling reactions in biomol. systems. Quantum-mech. (QM) methods are required for describing chem. reactions and other electronic processes, such as charge transfer or electronic excitation. However, QM methods are restricted to systems of up to a few hundred atoms. However, the size and conformational complexity of biopolymers calls for methods capable of treating up to several 100,000 atoms and allowing for simulations over time scales of tens of nanoseconds. This is achieved by highly efficient, force-field-based mol. mechanics (MM) methods. Thus to model large biomols. the logical approach is to combine the two techniques and, to use a QM method for the chem. active region (e.g., substrates and co-factors in an enzymic reaction) and an MM treatment for the surroundings (e.g., protein and solvent). The resulting schemes are commonly referred to as combined or hybrid QM/MM methods. They enable the modeling of reactive biomol. systems at a reasonable computational effort while providing the necessary accuracy.
- 46Huber, T.; Torda, A. E.; van Gunsteren, W. F. Local Elevation: A Method for Improving the Searching Properties of Molecular Dynamics Simulation. J. Comput.-Aided Mol. Des. 1994, 8, 695– 708, DOI: 10.1007/BF0012401646https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXjtVOnsrw%253D&md5=8d352c5753f9870081d4851ff12e58cdLocal elevation: a method for improving the searching properties of molecular dynamics simulationHuber, Thomas; Torda, Andrew E.; van Gunsteren, Wilfred F.Journal of Computer-Aided Molecular Design (1994), 8 (6), 695-708CODEN: JCADEQ; ISSN:0920-654X. (ESCOM)The concept of memory has been introduced into a mol. dynamics algorithm. This was done so as to persuade a mol. system to visit new areas of conformational space rather than be confined to a small no. of low-energy regions. The method is demonstrated on a simple model system and the 11-residue cyclic peptide cyclosporin A. For comparison, calcns. were also performed using simulated temp. annealing and a potential energy annealing scheme. Although the method can only be applied to systems with a small no. of degrees of freedom, it offers the chance to generate a multitude of different low-energy structures, where other methods only give a single one or few. This is clearly important in problems such as drug design, where one is interested in the conformational spread of a system.
- 47Laio, A.; Parrinello, M. Escaping Free-Energy Minima. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 12562– 12566, DOI: 10.1073/pnas.20242739947https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XnvFGiurc%253D&md5=48d5bc7436f3ef9d78369671e70fa608Escaping free-energy minimaLaio, Alessandro; Parrinello, MicheleProceedings of the National Academy of Sciences of the United States of America (2002), 99 (20), 12562-12566CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We introduce a powerful method for exploring the properties of the multidimensional free energy surfaces (FESs) of complex many-body systems by means of coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates. A characteristic feature of these dynamics is the presence of a history-dependent potential term that, in time, fills the min. in the FES, allowing the efficient exploration and accurate detn. of the FES as a function of the collective coordinates. We demonstrate the usefulness of this approach in the case of the dissocn. of a NaCl mol. in water and in the study of the conformational changes of a dialanine in soln.
- 48Christen, M.; van Gunsteren, W. F. On Searching in, Sampling of, and Dynamically Moving through Conformational Space of Biomolecular Systems: A Review. J. Comput. Chem. 2008, 29, 157– 166, DOI: 10.1002/jcc.2072548https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2sjktVOitQ%253D%253D&md5=c508200635d58b25f5ee678a9c016f87On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A reviewChristen Markus; van Gunsteren Wilfred FJournal of computational chemistry (2008), 29 (2), 157-66 ISSN:0192-8651.Methods to search for low-energy conformations, to generate a Boltzmann-weighted ensemble of configurations, or to generate classical-dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest.
- 49Bernardi, R. C.; Melo, M. C. R.; Schulten, K. Enhanced Sampling Techniques in Molecular Dynamics Simulations of Biological Systems. Biochim. Biophys. Acta, Gen. Subj. 2015, 1850, 872– 877, DOI: 10.1016/j.bbagen.2014.10.01949https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVanurbN&md5=44e3ac1aa042c35ee08aa86a6a63e78eEnhanced sampling techniques in molecular dynamics simulations of biological systemsBernardi, Rafael C.; Melo, Marcelo C. R.; Schulten, KlausBiochimica et Biophysica Acta, General Subjects (2015), 1850 (5), 872-877CODEN: BBGSB3; ISSN:0304-4165. (Elsevier B.V.)A review. Mol. dynamics has emerged as an important research methodol. covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local min. sepd. by high-energy barriers, which govern the biomol. motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange mol. dynamics, metadynamics and simulated annealing. Here the authors present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biol. systems and the choice of a suitable method is connected to biol. and phys. characteristics of the system, in particular system size. While metadynamics and replica-exchange mol. dynamics are the most adopted sampling methods to study biomol. dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromol. complexes. Mol. dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biol. function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of mol. dynamics.
- 50Shim, J.; MacKerell, A. D., Jr. Computational Ligand-Based Rational Design: Role of Conformational Sampling and Force Fields in Model Development. MedChemComm 2011, 2, 356– 370, DOI: 10.1039/c1md00044f50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Kht7c%253D&md5=70d822d1ca2faa484f723fb109597b77Computational ligand-based rational design: role of conformational sampling and force fields in model developmentShim, Jihyun; MacKerell, Alexander D., Jr.MedChemComm (2011), 2 (5), 356-370CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)A review. A significant no. of drug discovery efforts are based on natural products or high throughput screens from which compds. showing potential therapeutic effects are identified without knowledge of the target mol. or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compd.'s structure and physicochem. attributes to its biol. activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compds. with improved biol. attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quant. structure-activity relationships (QSAR) yielding quant. ests. of activities based on physiochem. properties, and to similarity searching, which explores compds. with similar properties as well as various combinations of the above. A no. of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is mol. mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression anal. to neural networks, from which the SAR is detd. Accordingly, for effective application of LBDD for SAR detns. it is important that the compds. be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modeling is largely based on use of the appropriate empirical force field for the mols. being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations assocd. with empirical energy functions and conformational sampling methods.
- 51Ballard, A. J.; Martiniani, S.; Stevenson, J. D.; Somani, S.; Wales, D. J. Exploiting the Potential Energy Landscape to Sample Free Energy. WIREs Comput. Mol. Sci. 2015, 5, 273– 289, DOI: 10.1002/wcms.1217There is no corresponding record for this reference.
- 52De Vivo, M.; Masetti, M.; Bottegoni, G.; Cavalli, A. Role of Molecular Dynamics and Related Methods in Drug Discovery. J. Med. Chem. 2016, 59, 4035– 4061, DOI: 10.1021/acs.jmedchem.5b0168452https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlWksLs%253D&md5=b3d8a4fb5705a3555c2bb2a962420396Role of Molecular Dynamics and Related Methods in Drug DiscoveryDe Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, AndreaJournal of Medicinal Chemistry (2016), 59 (9), 4035-4061CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)Mol. dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate est. of the thermodn. and kinetics assocd. with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theor. background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water mols. in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.
- 53Tsujishita, H.; Hirono, S. Camdas: An Automated Conformational Analysis System Using Molecular Dynamics. J. Comput.-Aided Mol. Des. 1997, 11, 305– 315, DOI: 10.1023/A:1007964913898There is no corresponding record for this reference.
- 54Wilson, S. R.; Cui, W.; Moskowitz, J. W.; Schmidt, K. E. Applications of Simulated Annealing to the Conformational Analysis of Flexible Molecules. J. Comput. Chem. 1991, 12, 342– 349, DOI: 10.1002/jcc.54012030754https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXitVKhsLw%253D&md5=7ca487c05c358c760a76eed13145b5deApplications of simulated annealing to the conformational analysis of flexible moleculesWilson, Stephen R.; Cui, Weili; Moskowitz, Jules W.; Schmidt, Kevin E.Journal of Computational Chemistry (1991), 12 (3), 342-9CODEN: JCCHDD; ISSN:0192-8651.A soln. to the global min. problem which uses the simulated annealing algorithm of Kirkpatrick is described. This method is a Metropolis (e-ΔE/kT) Monte Carlo sampling of conformation space with simultaneous constraint of the search by lowering the temp. T so that the search converges on the global min. The Anneal-Conformer program has been extensively tested with peptides and org. mols. using either the Amber or MM2 force fields. A history file of the simulated annealing process allows reconstruction of the random walk in conformation space for subsequent examn. Thus plots of distance and dihedral angle changes during the search for the global min. can be examd. to deduce mol. shape and flexibility. A sep. program Conf-Gen reads the history file and exts. all low energy conformations visited during the run.
- 55Sperandio, O.; Souaille, M.; Delfaud, F.; Miteva, M. A.; Villoutreix, B. O. MED-3DMC: A New Tool to Generate 3D Conformation Ensembles of Small Molecules with a Monte Carlo Sampling of the Conformational Space. Eur. J. Med. Chem. 2009, 44, 1405– 1409, DOI: 10.1016/j.ejmech.2008.09.05255https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjtVSjtLw%253D&md5=bc3b0f5ea5b23da6eec7048f39081448MED-3DMC: A new tool to generate 3D conformation ensembles of small molecules with a Monte Carlo sampling of the conformational spaceSperandio, Olivier; Souaille, Marc; Delfaud, Francois; Miteva, Maria A.; Villoutreix, Bruno O.European Journal of Medicinal Chemistry (2009), 44 (4), 1405-1409CODEN: EJMCA5; ISSN:0223-5234. (Elsevier Masson SAS)Obtaining an efficient sampling of the low to medium energy regions of a ligand conformational space is of primary importance for getting insight into relevant binding modes of drug candidates, or for the screening of rigid mol. entities on the basis of a predefined pharmacophore or for rigid body docking. Here, we report the development of a new computer tool that samples the conformational space by using the Metropolis Monte Carlo algorithm combined with the MMFF94 van der Waals energy term. The performances of the program have been assessed on 86 drug-like mols. that resulted from an ADME/tox profiling applied on cocrystalized small mols. and were compared with the program Omega on the same dataset. Our program has also been assessed on the 85 mols. of the Astex diverse set. Both test sets show convincing performance of our program at sampling the conformational space.
- 56Grebner, C.; Becker, J.; Stepanenko, S.; Engels, B. Efficiency of Tabu-Search-Based Conformational Search Algorithms. J. Comput. Chem. 2011, 32, 2245– 2253, DOI: 10.1002/jcc.21807There is no corresponding record for this reference.
- 57Shang, C.; Liu, Z.-P. Stochastic Surface Walking Method for Structure Prediction and Pathway Searching. J. Chem. Theory Comput. 2013, 9, 1838– 1845, DOI: 10.1021/ct301010b57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOlt7c%253D&md5=ff2585b886e8cc63d4443934f5317048Stochastic Surface Walking Method for Structure Prediction and Pathway SearchingShang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (3), 1838-1845CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We propose an unbiased general-purpose potential energy surface (PES) searching method for both the structure and the pathway prediction of a complex system. The method is based on the idea of bias-potential-driven dynamics and Metropolis Monte Carlo. A central feature of the method is able to perturb smoothly a structural configuration toward a new configuration and simultaneously has the ability to surmount the high barrier in the path. We apply the method for locating the global min. (GM) of short-ranged Morse clusters up to 103 atoms starting from a random structure without using extra information from the system. In addn. to GM searching, the method can identify the pathways for chem. reactions with large dimensionality, as demonstrated in a nanohelix transformation contg. 222 degrees of freedoms.
- 58Zhang, X.-J.; Shang, C.; Liu, Z.-P. From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex Material. J. Chem. Theory Comput. 2013, 9, 3252– 3260, DOI: 10.1021/ct400238j58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXosVegsr0%253D&md5=0e94b080ff99b33134c703b183357f15From Atoms to Fullerene: Stochastic Surface Walking Solution for Automated Structure Prediction of Complex MaterialZhang, Xiao-Jie; Shang, Cheng; Liu, Zhi-PanJournal of Chemical Theory and Computation (2013), 9 (7), 3252-3260CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)It is of general concern whether the automated structure prediction of unknown material without recourse to any knowledge from expt. is ever possible considering the daunting complexity of potential energy surface (PES) of material. Here we demonstrate that the stochastic surface walking (SSW) method can be a general and promising soln. to this ultimate goal, which is applied to assemble carbon fullerenes contg. up to 100 atoms (including 60, 70, 76, 78, 80, 84, 90, 96, and 100 atoms) from randomly distributed atoms, a long-standing challenge in global optimization. Combining the SSW method with a parallel replica exchange algorithm, we can locate the global min. (GM) of these large fullerenes efficiently without being trapped in numerous energy-nearly degenerate isomers. Detailed analyses on the SSW trajectories allow us to rationalize how and why the SSW method is able to explore the highly complex PES, which highlights the abilities of SSW method for surmounting the high barrier and the preference of SSW trajectories to the low energy pathways. The work demonstrates that the parallel SSW method is a practical tool for predicting unknown materials.
- 59Shang, C.; Zhang, X.-J.; Liu, Z.-P. Stochastic Surface Walking Method for Crystal Structure and Phase Transition Pathway Prediction. Phys. Chem. Chem. Phys. 2014, 16, 17845– 17856, DOI: 10.1039/C4CP01485E59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyms7jE&md5=c5dc152fa492d8978d79bbcf35313753Stochastic surface walking method for crystal structure and phase transition pathway predictionShang, Cheng; Zhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2014), 16 (33), 17845-17856CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The detn. of crystal structures and the solid-to-solid phase transition mechanisms are two important and related subjects in material science. Here we develop an unbiased general-purpose potential energy surface (PES) searching method, namely, SSW-crystal method, for prediction of both the crystal structure and the crystal phase transition pathway. The SSW-crystal method features with stochastic surface walking (SSW) via repeated small structural perturbation by taking into account the second deriv. information on both the lattice and the atom degrees of freedom. The SSW-crystal method is capable of overcoming the high barrier of phase transition and identifying the desirable phase transition reaction coordinates. By applying the SSW-crystal method to a set of examples, including SiO2 crystal up to 162 atoms per cell, Lennard-Jones model crystals up to 256 atoms, ternary SrTiO3 crystal of 50 atoms and the rutile-to-anatase TiO2 phase transition, we show that the SSW-crystal method can efficiently locate the global min. (GM) from random initial structures without a priori knowledge of the system, and also allows for exhaustive sampling of the phase transition pathways, from which the lowest energy pathway can be obtained.
- 60Zhang, X.-J.; Liu, Z.-P. Reaction Sampling and Reactivity Prediction Using the Stochastic Surface Walking Method. Phys. Chem. Chem. Phys. 2015, 17, 2757– 2769, DOI: 10.1039/C4CP04456H60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVSgur3F&md5=c5ac6082903ea35d005a1e00ab73febeReaction sampling and reactivity prediction using the stochastic surface walking methodZhang, Xiao-Jie; Liu, Zhi-PanPhysical Chemistry Chemical Physics (2015), 17 (4), 2757-2769CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The prediction of chem. reactivity and thus the design of new reaction systems are the key challenges in chem. Here, we develop an unbiased general-purpose reaction sampling method, the stochastic surface walking based reaction sampling (SSW-RS) method, and show that the new method is a promising soln. for reactivity prediction of complex reaction systems. The SSW-RS method is capable of sampling both the configuration space of the reactant and the reaction space of pathways, owing to the combination of two recently developed theor. methods, namely, the stochastic surface walking (SSW) method for potential energy surface (PES) exploration and the double-ended surface walking (DESW) method for building pathways. By integrating with first principles calcns., we show that the SSW-RS method can be applied to investigate the kinetics of complex org. reactions featuring many possible reaction channels and complex hydrogen-bonding networks, as demonstrated here using two examples, epoxypropane hydrolysis in aq. soln. and β-D-glucopyranose decompn. Our results show that simultaneous sampling of the soft hydrogen-bonding conformations and the chem. reactions involving hard bond making/breaking can be achieved in the SSW-RS simulation, and the mechanism and kinetics can be predicted without a priori information on the system. Unexpected new chem. for these reactions is revealed and discussed. In particular, despite many possible pathways for β-D-glucopyranose decompn., the SSW-RS shows that only β-D-glucose and levoglucosan are kinetically preferred direct products and the 5- or 7-member ring products should be secondary products derived from β-D-glucose or levoglucosan. As a general tool for reactivity prediction, the SSW-RS opens a new route for the design of rational reactions.
- 61Vázquez, S. A.; Martínez-Núñez, E. HCN Elimination from Vinyl Cyanide: Product Energy Partitioning, the Role of Hydrogen–Deuterium Exchange Reactions and a New Pathway. Phys. Chem. Chem. Phys. 2015, 17, 6948– 6955, DOI: 10.1039/C4CP05626D61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXit1aquro%253D&md5=7d4dd3daa6fd88d8777f26838c395778HCN elimination from vinyl cyanide: product energy partitioning, the role of hydrogen-deuterium exchange reactions and a new pathwayVazquez, Saulo A.; Martinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (10), 6948-6955CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The different HCN elimination pathways from vinyl cyanide (VCN) are studied in this paper using RRKM, Kinetic Monte Carlo (KMC), and quasi-classical trajectory (QCT) calcns. A new HCN elimination pathway proves to be very competitive with the traditional 3-center and 4-center mechanisms, particularly at low excitation energies. However, low excitation energies have never been exptl. explored, and the high and low excitation regions are dynamically different. The KMC simulations carried out using singly deuterated VCN (CH2=CD-CN) at 148 kcal mol-1 show the importance of hydrogen-deuterium exchange reactions: both DCN and HCN will be produced in any of the 1,1 and 1,2 elimination pathways. The QCT simulation results obtained for the 3-center pathway are in agreement with the available exptl. results, with the 4-center results showing much more excitation of the products. In general, results seem to be consistent with a photodissocn. mechanism at 193 nm, where the mol. dissocs. (at least the HCN elimination pathways) in the ground electronic state. However, simulations assume that internal conversion is a fully statistical process, i.e., the HCN elimination channels proceed on the ground electronic state according to RRKM theory, which might not be the case. In future studies it would be of interest to include the photo-prepd. electronically excited state(s) in the dynamics simulations.
- 62Martínez-Núñez, E. An Automated Method to Find Transition States Using Chemical Dynamics Simulations. J. Comput. Chem. 2015, 36, 222– 234, DOI: 10.1002/jcc.2379062https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGgtLbO&md5=e22946d4913acb912ffd139e36d6c11cAn automated method to find transition states using chemical dynamics simulationsMartinez-Nunez, EmilioJournal of Computational Chemistry (2015), 36 (4), 222-234CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A procedure to automatically find the transition states (TSs) of a mol. system (MS) is proposed. It has two components: high-energy chem. dynamics simulations (CDS), and an algorithm that analyzes the geometries along the trajectories to find reactive pathways. Two levels of electronic structure calcns. are involved: a low level (LL) is used to integrate the trajectories and also to optimize the TSs, and a higher level (HL) is used to reoptimize the structures. The method has been tested in three MSs: formaldehyde, formic acid (FA), and vinyl cyanide (VC), using MOPAC2012 and Gaussian09 to run the LL and HL calcns., resp. Both the efficacy and efficiency of the method are very good, with around 15 TS structures optimized every 10 trajectories, which gives a total of 7, 12, and 83 TSs for formaldehyde, FA, and VC, resp. The use of CDS makes it a powerful tool to unveil possible nonstatistical behavior of the system under study. © 2014 Wiley Periodicals, Inc.
- 63Martínez-Núñez, E. An Automated Transition State Search Using Classical Trajectories Initialized at Multiple Minima. Phys. Chem. Chem. Phys. 2015, 17, 14912– 14921, DOI: 10.1039/C5CP02175H63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnslOqsLo%253D&md5=695f6ea8566cc28afe6bb7c89a434bbeAn automated transition state search using classical trajectories initialized at multiple minimaMartinez-Nunez, EmilioPhysical Chemistry Chemical Physics (2015), 17 (22), 14912-14921CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Very recently, we proposed an automated method for finding transition states of chem. reactions using dynamics simulations; the method has been termed Transition State Search using Chem. Dynamics Simulations (TSSCDS) (E. Martinez-Nunez, J. Comput. Chem., 2015, 36, 222-234). In the present work, an improved automated search procedure is developed, which consists of iteratively running different ensembles of trajectories initialized at different min. The iterative TSSCDS method is applied to the complex C3H4O system, obtaining a total of 66 different min. and 276 transition states. With the obtained transition states and paths, statistical RRKM calcns. and Kinetic Monte Carlo simulations are carried out to study the fragmentation dynamics of propenal, which is the global min. of the system. The kinetic simulations provide a (three-body dissocn.)/(CO elimination) ratio of 1.49 for an excitation energy of 148 kcal mol-1, which agrees well with the corresponding value obtained in the photolysis of propenal at 193 nm (1.1), suggesting that at least these two channels: three-body dissocn. (to give H2 + CO + C2H2) and CO elimination occur on the ground electronic state.
- 64Varela, J. A.; Vázquez, S. A.; Martínez-Núñez, E. An Automated Method to Find Reaction Mechanisms and Solve the Kinetics in Organometallic Catalysis. Chem. Sci. 2017, 8, 3843– 3851, DOI: 10.1039/C7SC00549K64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjsl2rtr8%253D&md5=df77d0eab3dac5fc42530661b1d57954An automated method to find reaction mechanisms and solve the kinetics in organometallic catalysisVarela, J. A.; Vazquez, S. A.; Martinez-Nunez, E.Chemical Science (2017), 8 (5), 3843-3851CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)A novel computational method is proposed in this work for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions. The method does not rely on either chem.intuition or assumed a priori mechanisms, and it works in a fully automated fashion. Its core is a procedure, recently developed by one of the authors, that combines accelerated direct dynamics with an efficient geometry-based post-processing algorithm to find transition states. In the present work, several auxiliary tools have been added to deal with the specific features of transition metal catalytic reactions. As a test case, we chose the cobalt-catalyzed hydroformylation of ethylene because of its well-established mechanism, and the fact that it has already been used in previous automated computational studies. Besides the generally accepted mechanism of Heck and Breslow, several side reactions, such as hydrogenation of the alkene, emerged from our calcns. Addnl., the calcd.rate law for the hydroformylation reaction agrees reasonably well with those obtained in previous exptl.and theor.studies.
- 65Rodriguez, A.; Rodriguez-Fernandez, R.; Vazquez, S. A.; Barnes, G. L.; Stewart, J. J. P.; Martinez-Nunez, E. tsscds2018: A Code for Automated Discovery of Chemical Reaction Mechanisms and Solving the Kinetics. J. Comput. Chem. 2018, 39, 1922– 1930, DOI: 10.1002/jcc.2537065https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslOksr7J&md5=f0374c367acd28cb3cf2ebedb5ef3eeetsscds2018: A code for automated discovery of chemical reaction mechanisms and solving the kineticsRodriguez, Aurelio; Rodriguez-Fernandez, Roberto; A. Vazquez, Saulo; L. Barnes, George; J. P. Stewart, James; Martinez-Nunez, EmilioJournal of Computational Chemistry (2018), 39 (23), 1922-1930CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)A new software, called tsscds2018, has been developed to discover reaction mechanisms and solve the kinetics in a fully automated fashion. The program employs algorithms based on Graph Theory to find transition state (TS) geometries from accelerated semiempirical dynamics simulations carried out with MOPAC2016. Then, the TSs are connected to the corresponding min. and the reaction network is obtained. Kinetic data like populations vs time or the abundancies of each product can also be obtained with our program thanks to a Kinetic Monte Carlo routine. Highly accurate ab initio potential energy diagrams and kinetics can also be obtained using an interface with Gaussian09. The source code is available on the following site: © 2018 Wiley Periodicals, Inc.
- 66Cerjan, C. J.; Miller, W. H. On Finding Transition States. J. Chem. Phys. 1981, 75, 2800– 2806, DOI: 10.1063/1.44235266https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3MXltlyqsrY%253D&md5=62bc3d736a49a1df81c3f7b428117645On finding transition statesCerjan, Charles J.; Miller, William H.Journal of Chemical Physics (1981), 75 (6), 2800-6CODEN: JCPSA6; ISSN:0021-9606.An algorithm for locating transition states on a potential energy surface is described. The most important feature of the algorithm, which makes explicit use of the second deriv. matrix of the potential surface, is that it is able to "walk uphill" from the min. on a potential surface to the transition state essentially automatically. The method is illustrated by application to a two dimensional model problem, to the vinylidene-acetylene rearrangement (H2C = C:↔HC≡CH), and to the dissocn. and rearrangement of formaldehyde (H2CO↔H2 + O, HCOH). The algorithm is also seen to provide an improved way of following a reaction path from a transition state down to reactants or products.
- 67Simons, J.; Joergensen, P.; Taylor, H.; Ozment, J. Walking on Potential Energy Surfaces. J. Phys. Chem. 1983, 87, 2745– 2753, DOI: 10.1021/j100238a01367https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3sXksF2it74%253D&md5=af251d7a8647c328879862fd7cde68a3Walking on potential energy surfacesSimons, Jack; Joergensen, Poul; Taylor, Hugh; Ozment, JudyJournal of Physical Chemistry (1983), 87 (15), 2745-53CODEN: JPCHAX; ISSN:0022-3654.By combining a local quadratic approxn. to the potential energy surface with the concept of a trust radius within which this quadratic approxn. is accurate and a scaling of one active coordinate, an automated surface walking algorithm was developed. This algorithm allows one to walk from geometries characteristic of equil. mol. structures, uphill along stream beds, through transition-state geometries, and onward to product-mol. equil. geometries. The method was appled to model and ab initio test cases with encouraging results. The success of using the algorithm in connection with approx. Hessian matrixes formed via so-called update techniques, which require only local force information, is esp. encouraging in light of the high cost of ab initio anal. evaluation of the Hessian.
- 68Davis, H. L.; Wales, D. J.; Berry, R. S. Exploring Potential Energy Surfaces with Transition State Calculations. J. Chem. Phys. 1990, 92, 4308– 4319, DOI: 10.1063/1.45779068https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXit1elu74%253D&md5=c2ae2665bcc5e23802f289641cd94e3cExploring potential energy surfaces with transition state calculationsDavis, Heidi L.; Wales, David J.; Berry, R. StephenJournal of Chemical Physics (1990), 92 (7), 4308-19CODEN: JCPSA6; ISSN:0021-9606.Means are presented for using stationary points in two ways. One, for well-understood potentials, elucidates relations between the form of the surface and the dynamics that it supports, including the detn. of the effective mol. symmetry group. The other, for potentials of uncertain quality, provides a test for unphys. characteristics and suggests how the surface might be improved if it is found to be unsatisfactory in some respect. Our approach involves comparison of transition-state calcns. using the slowest-slide and Cerjan-Miller algorithms for two systems: the Lennard-Jones Ar7 cluster, and the Handy-Carter many-body-expansion potential for the ground state of formaldehyde.
- 69Wales, D. J. Basins of Attraction for Stationary Points on a Potential-Energy Surface. J. Chem. Soc., Faraday Trans. 1992, 88, 653– 657, DOI: 10.1039/ft9928800653There is no corresponding record for this reference.
- 70Wales, D. J. Locating Stationary Points for Clusters in Cartesian Coordinates. J. Chem. Soc., Faraday Trans. 1993, 89, 1305– 1313, DOI: 10.1039/ft993890130570https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXksFKmu78%253D&md5=b823814bb89c8e62b4e904ae2d37b45dLocating stationary points for clusters in cartesian coordinatesWales, David J.Journal of the Chemical Society, Faraday Transactions (1993), 89 (9), 1305-13,4 platesCODEN: JCFTEV; ISSN:0956-5000.Location of min. and transition states on a potential energy surface by the eigenvector-following method using Cartesian coordinates and a projection operator is described. Comparisons with calcns. employing std. internal coordinates are made for a wide variety of model clusters. The new method, suggested by Baker and Hehre (1991), generally produces faster convergence and solves a no. of problems that are inherent when using distance, bond angle, and dihedral angle internal coordinates. In particular, eigenvector-following calcns. using analytic first and second energy derivs. should now be possible for much larger systems. Some example reaction paths are illustrated, including a new facetting rearrangement of 55- and 147-atom Mackay icosahedra. The basins of attraction of min. and transition states are also calcd., i.e., the regions of the potential-energy surface for which stationary-point searches converge to a given structure. The superiority of the projection operator approach is again demonstrated, and the previous observation that initial geometrical contraction is helpful in transition-state searches is confirmed.
- 71Jensen, F. Locating Transition Structures by Mode Following: A Comparison of Six Methods on the Ar8Lennard-Jones Potential. J. Chem. Phys. 1995, 102, 6706– 6718, DOI: 10.1063/1.469144There is no corresponding record for this reference.
- 72Doye, J. P. K.; Wales, D. J. Surveying a Potential Energy Surface by Eigenvector-Following. Z. Phys. D: At., Mol. Clusters 1997, 40, 194– 197, DOI: 10.1007/s00460005019272https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXjs12rtrw%253D&md5=affb326a8ca9636d1e24e1b5937b840eSurveying a potential energy surface by eigenvector-following. Applications to global optimization and the structural transformations of clustersDoye, J. P. K.; Wales, D. J.Zeitschrift fuer Physik D: Atoms, Molecules and Clusters (1997), 40 (1-4), 194-197CODEN: ZDACE2; ISSN:0178-7683. (Springer)We have developed a method to search potential energy surfaces which avoids some of the difficulties assocd. with trapping in local min. Steps are directly taken between min. using eigenvector-following. Exploration of this space by low temp. Metropolis Monte Carlo is a useful global optimization tool. This method successfully finds the lowest energy icosahedral min. of Lennard-Jones clusters from random starting configurations, but cannot find the global min. in a reasonable time for difficult cases such as the 38-atom Lennard-Jones cluster where the face-centered-cubic truncated octahedron is lowest in energy. However, by performing searches at higher temps., we have found a pathway between the truncated octahedron and the lowest energy icosahedral min. Such a pathway may be illustrative of some of the structural transformations that are obsd. for supported metal clusters by electron microscopy.
- 73Broyden, C. G. Quasi-Newton Methods and Their Application to Function Minimisation. Math. Comp. 1967, 21, 368– 381, DOI: 10.1090/S0025-5718-1967-0224273-2There is no corresponding record for this reference.
- 74Munro, L. J.; Wales, D. J. Defect Migration in Crystalline Silicon. Phys. Rev. B: Condens. Matter Mater. Phys. 1999, 59, 3969– 3980, DOI: 10.1103/PhysRevB.59.396974https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXosVeltw%253D%253D&md5=a958a13eef54db0261a60a64d4e77e87Defect migration in crystalline siliconMunro, Lindsey J.; Wales, David J.Physical Review B: Condensed Matter and Materials Physics (1999), 59 (6), 3969-3980CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)A no. of vacancy and interstitial defect migration mechanisms were characterized for cryst. Si using supercells contg. 64 and 216 atoms and a tight-binding approach. The authors study various defect configurations corresponding to min. and the pathways that connect them. A modified eigenvector-following approach was used to locate true transition states. The authors exploit the fact that only one Hessian eigenvector is needed to define the uphill search direction and use conjugate gradient minimization in the tangent space to produce a hybrid algorithm. Two implementations of this approach are considered, the 1st where 2nd derivs. are available but full diagonalization of the Hessian would be the most time-consuming step, and the 2nd where only 1st derivs. of the energy are known.
- 75Malek, R.; Mousseau, N. Dynamics of Lennard-Jones Clusters: A Characterization of the Activation-Relaxation Technique. Phys. Rev. E: Stat. Phys., Plasmas, Fluids, Relat. Interdiscip. Top. 2000, 62, 7723– 7728, DOI: 10.1103/PhysRevE.62.772375https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXoslahurw%253D&md5=73391e2c5502b4312a8cdd0f07852b91Dynamics of Lennard-Jones clusters: A characterization of the activation-relaxation techniqueMalek, Rachid; Mousseau, NormandPhysical Review E: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics (2000), 62 (6-A), 7723-7728CODEN: PLEEE8; ISSN:1063-651X. (American Physical Society)The potential energy surface of Lennard-Jones clusters is investigated using the activation-relaxation technique (ART). This method defines events in the configurational energy landscape as a two-step process: (a) a configuration is first activated from a local min. to a nearby saddle-point, and (b) is then relaxed to a new min. Although ART has been applied with success to a wide range of materials such as a-Si, a-SiO2, and binary Lennard-Jones glasses, questions remain regarding the biases of the technique. We address some of these questions in a detailed study of ART-generated events in Lennard-Jones clusters, a system for which much is already known. In particular, we study the distribution of saddle-points, the pathways between configurations, and the reversibility of paths. We find that ART can identify all trajectories with a first-order saddle point leaving a given min., is fully reversible, and samples events following the Boltzmann wt. at the saddle point.
- 76Deglmann, P.; Furche, F. Efficient Characterization of Stationary Points on Potential Energy Surfaces. J. Chem. Phys. 2002, 117, 9535– 9538, DOI: 10.1063/1.152339376https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XovVSru78%253D&md5=3bbd5b3b826d7210588dbb7121b72176Efficient characterization of stationary points on potential energy surfacesDeglmann, Peter; Furche, FilippJournal of Chemical Physics (2002), 117 (21), 9535-9538CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Traditional methods for characterizing an optimized mol. structure as a min. or as a saddle point on the nuclear potential energy surface require the full Hessian. However, if f denotes the no. of nuclear degrees of freedom, a full Hessian calcn. is more expensive than a single point geometry optimization step by the order of magnitude of f. Here we present a method which allows to det. the lowest vibrational frequencies of a mol. at significantly lower cost. Our approach takes advantage of the fact that only a few perturbed first-order wave functions need to be computed in an iterative diagonalization scheme instead of f ones in a full Hessian calcn. We outline an implementation for Hartree-Fock and d. functional methods. Applications indicate a scaling similar to that of a single point energy or gradient calcn., but with a larger prefactor. Depending on the no. of soft vibrational modes, the iterative method becomes effective for systems with more than 30-50 atoms.
- 77Reiher, M.; Neugebauer, J. A Mode-Selective Quantum Chemical Method for Tracking Molecular Vibrations Applied to Functionalized Carbon Nanotubes. J. Chem. Phys. 2003, 118, 1634– 1641, DOI: 10.1063/1.152390877https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjtVaquw%253D%253D&md5=616ea82fd0a616e1c7c6428c4581da7bA mode-selective quantum chemical method for tracking molecular vibrations applied to functionalized carbon nanotubesReiher, Markus; Neugebauer, JohannesJournal of Chemical Physics (2003), 118 (4), 1634-1641CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The theor. investigation of mesoscopic objects requires new techniques which are particularly suited for the study of selected aspects of these systems. Vibrational spectroscopy is a main source for structural information on heterogeneous systems. We present an efficient quantum chem. method, which relies on a modified Davidson algorithm for targeting selected vibrations in IR and Raman spectra. This approach is applied to the characteristic breathing modes of single-walled carbon nanotubes.
- 78Sharada, S. M.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Automated Transition State Searches without Evaluating the Hessian. J. Chem. Theory Comput. 2012, 8, 5166– 5174, DOI: 10.1021/ct300659dThere is no corresponding record for this reference.
- 79Bergeler, M.; Herrmann, C.; Reiher, M. Mode-Tracking Based Stationary-Point Optimization. J. Comput. Chem. 2015, 36, 1429– 1438, DOI: 10.1002/jcc.2395879https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpvFWgt7c%253D&md5=50ae502b58d1b2eb8f04225407e085afMode-tracking based stationary-point optimizationBergeler, Maike; Herrmann, Carmen; Reiher, MarkusJournal of Computational Chemistry (2015), 36 (19), 1429-1438CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)In this work, we present a transition-state optimization protocol based on the Mode-Tracking algorithm [Reiher and Neugebauer, J. Chem. Phys., 2003, 118, 1634]. By calcg. only the eigenvector of interest instead of diagonalizing the full Hessian matrix and performing an eigenvector following search based on the selectively calcd. vector, we can efficiently optimize transition-state structures. The initial guess structures and eigenvectors are either chosen from a linear interpolation between the reactant and product structures, from a nudged-elastic band search, from a constrained-optimization scan, or from the min.-energy structures. Alternatively, initial guess vectors based on chem. intuition may be defined. We then iteratively refine the selected vectors by the Davidson subspace iteration technique. This procedure accelerates finding transition states for large mols. of a few hundred atoms. It is also beneficial in cases where the starting structure is very different from the transition-state structure or where the desired vector to follow is not the one with lowest eigenvalue. Explorative studies of reaction pathways are feasible by following manually constructed mol. distortions. © 2015 Wiley Periodicals, Inc.
- 80Halgren, T. A.; Lipscomb, W. N. The Synchronous-Transit Method for Determining Reaction Pathways and Locating Molecular Transition States. Chem. Phys. Lett. 1977, 49, 225– 232, DOI: 10.1016/0009-2614(77)80574-580https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXlsFWmtLs%253D&md5=90c0d95b096220fddcc7eebc0639fdfdThe synchronous-transit method for determining reaction pathways and locating molecular transition statesHalgren, Thomas A.; Lipscomb, William N.Chemical Physics Letters (1977), 49 (2), 225-32CODEN: CHPLBC; ISSN:0009-2614.In the synchronous-transit method, a model linear synchronous transit pathway is first constructed and is then refined by optimizing 1 or more intermediate structures subject to the constraint that the optimized structure retain the same relative position along the path orthogonal optimization. The method yields a series of energy ests. which progressively bound the energy of the transition state from above and from below. High computational efficiency is attainable, and sufficient flexibility is provided to deal with asynchronous processes. Comparisons are made to the alternative reaction-coordinate approach. The method is applied to a model 2-dimensional energy surface and to the allowed electrocyclic interconversions of the cyclopropyl and allyl cations and of cyclobutene and cis-butadiene.
- 81Ayala, P. Y.; Schlegel, H. B. A Combined Method for Determining Reaction Paths, Minima, and Transition State Geometries. J. Chem. Phys. 1997, 107, 375– 384, DOI: 10.1063/1.47439881https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXksVeksrY%253D&md5=2ec17a4bf9a0f0f848e6fe0b844fe250A combined method for determining reaction paths, minima, and transition state geometriesAyala, Philippe Y.; Schlegel, H. BernhardJournal of Chemical Physics (1997), 107 (2), 375-384CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Mapping out a reaction mechanism involves optimizing the reactants and products, finding the transition state and following the reaction path connecting them. Transition states can be difficult to locate and reaction paths can be expensive to follow. We describe an efficient algorithm for detg. the transition state, min. and reaction path in a single procedure. Starting with an approx. path represented by N points, the path is iteratively relaxed until one of the N points reached the transition state, the end points optimize to min. and the remaining points converged to a second order approxn. of the steepest descent path. The method appears to be more reliable than conventional transition state optimization algorithms, and requires only energies and gradients, but not second deriv. calcns. The procedure is illustrated by application to a no. of model reactions. In most cases, the reaction mechanism can be described well using 5 to 7 points to represent the transition state, the min. and the path. The computational cost of relaxing the path is less than or comparable to the cost of std. techniques for finding the transition state and the min., detg. the transition vector and following the reaction path on both sides of the transition state.
- 82Henkelman, G.; Jónsson, H. A Dimer Method for Finding Saddle Points on High Dimensional Potential Surfaces Using Only First Derivatives. J. Chem. Phys. 1999, 111, 7010– 7022, DOI: 10.1063/1.48009782https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXmt1Ojurc%253D&md5=d3628bc9e56615b91730dd2224a36723A dimer method for finding saddle points on high dimensional potential surfaces using only first derivativesHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (1999), 111 (15), 7010-7022CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The problem of detg. which activated (and slow) transitions can occur from a given initial state at a finite temp. is addressed. In the harmonic approxn. to transition state theory this problem reduces to finding the set of low lying saddle points at the boundary of the potential energy basin assocd. with the initial state, as well as the relevant vibrational frequencies. Also, when full transition state theory calcns. are carried out, it can be useful to know the location of the saddle points on the potential energy surface. A method for finding saddle points without knowledge of the final state of the transition is described. The method only makes use of first derivs. of the potential energy and is, therefore, applicable in situations where second derivs. are too costly or too tedious to evaluate, for example, in plane wave based d. functional theory calcns. It is also designed to scale efficiently with the dimensionality of the system and can be applied to very large systems when empirical or semiempirical methods are used to obtain the at. forces. The method can be started from the potential min. representing the initial state, or from an initial guess closer to the saddle point. An application to Al adatom diffusion on an Al(100) surface described by an embedded atom method potential is presented. A large no. of saddle points were found for adatom diffusion and dimer/vacancy formation. A surprisingly low energy four atom exchange process was found as well as processes indicative of local hex reconstruction of the surface layer.
- 83Henkelman, G.; Uberuaga, B. P.; Jónsson, H. A Climbing Image Nudged Elastic Band Method for Finding Saddle Points and Minimum Energy Paths. J. Chem. Phys. 2000, 113, 9901– 9904, DOI: 10.1063/1.132967283https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagurc%253D&md5=3899b9e2e9e3eb74009987d96623f018A climbing image nudged elastic band method for finding saddle points and minimum energy pathsHenkelman, Graeme; Uberuaga, Blas P.; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9901-9904CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)A modification of the nudged elastic band method for finding min. energy paths is presented. One of the images is made to climb up along the elastic band to converge rigorously on the highest saddle point. Also, variable spring consts. are used to increase the d. of images near the top of the energy barrier to get an improved est. of the reaction coordinate near the saddle point. Applications to CH4 dissociative adsorption on Ir(111) and H2 on Si(100) using plane wave based d. functional theory are presented.
- 84Henkelman, G.; Jónsson, H. Improved Tangent Estimate in the Nudged Elastic Band Method for Finding Minimum Energy Paths and Saddle Points. J. Chem. Phys. 2000, 113, 9978– 9985, DOI: 10.1063/1.132322484https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFagu7Y%253D&md5=57dbeadabf6061460912090f40b581e0Improved tangent estimate in the nudged elastic band method for finding minimum energy paths and saddle pointsHenkelman, Graeme; Jonsson, HannesJournal of Chemical Physics (2000), 113 (22), 9978-9985CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)An improved way of estg. the local tangent in the nudged elastic band method for finding min. energy paths is presented. In systems where the force along the min. energy path is large compared to the restoring force perpendicular to the path and when many images of the system are included in the elastic band, kinks can develop and prevent the band from converging to the min. energy path. We show how the kinks arise and present an improved way of estg. the local tangent which solves the problem. The task of finding an accurate energy and configuration for the saddle point is also discussed and examples given where a complementary method, the dimer method, is used to efficiently converge to the saddle point. Both methods only require the first deriv. of the energy and can, therefore, easily be applied in plane wave based d.-functional theory calcns. Examples are given from studies of the exchange diffusion mechanism in a Si crystal, Al addimer formation on the Al(100) surface, and dissociative adsorption of CH4 on an Ir(111) surface.
- 85Maragakis, P.; Andreev, S. A.; Brumer, Y.; Reichman, D. R.; Kaxiras, E. Adaptive Nudged Elastic Band Approach for Transition State Calculation. J. Chem. Phys. 2002, 117, 4651– 4658, DOI: 10.1063/1.149540185https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmsVWntbo%253D&md5=9645dcee50aacfef2aa9265a1989ac1eAdaptive nudged elastic band approach for transition state calculationMaragakis, P.; Andreev, Stefan A.; Brumer, Yisroel; Reichman, David R.; Kaxiras, EfthimiosJournal of Chemical Physics (2002), 117 (10), 4651-4658CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)We present a method for the location of transition states in complicated phys. systems. Our algorithm is a variation of the well-established nudged elastic band method and leads to significant improvements in efficiency and accuracy. We assess the applicability of our method by testing it on several systems of practical interest representing a variety of phys. situations. At the mol. level, we apply the method to tautomerization processes in nucleic acid bases and the double proton transfer in nucleic acid base pairs. For bulk systems, we considered the concerted exchange mechanism in Si, which is a complicated pathway for defect-free diffusion in the diamond lattice. For surface systems, we considered ad-dimer diffusion mechanisms on Si(100). We incorporated the climbing image extension of the nudged elastic band method and compared it against the original approach on two-dimensional model potential energy surfaces. Based on favorable comparisons with related methods and the general implementation of our method, we believe that this is well suited for efficient ests. of activation barriers with sophisticated electronic structure codes.
- 86E, W.; Ren, W.; Vanden-Eijnden, E. String Method for the Study of Rare Events. Phys. Rev. B: Condens. Matter Mater. Phys. 2002, 66, 052301, DOI: 10.1103/PhysRevB.66.05230186https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmvVSlurg%253D&md5=1c24a86bf403c333e9705f00876e4aa3String method for the study of rare eventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricPhysical Review B: Condensed Matter and Materials Physics (2002), 66 (5), 052301/1-052301/4CODEN: PRBMDO; ISSN:0163-1829. (American Physical Society)We present an efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e., smooth curves with intrinsic parametrization whose dynamics takes them to the most probable transition path between two metastable regions in configuration space. Free energy barriers and transition rates can then be detd. by a std. umbrella sampling around the string. Applications to Lennard-Jones cluster rearrangement and thermally induced switching of a magnetic film are presented.
- 87E, W.; Ren, W.; Vanden-Eijnden, E. Finite Temperature String Method for the Study of Rare Events. J. Phys. Chem. B 2005, 109, 6688– 6693, DOI: 10.1021/jp045543087https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFSnsbo%253D&md5=f92a743d5d4b946756c04c6c1cbc8a8dFinite Temperature String Method for the Study of Rare EventsE, Weinan; Ren, Weiqing; Vanden-Eijnden, EricJournal of Physical Chemistry B (2005), 109 (14), 6688-6693CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)A method is presented for the study of rare events such as conformational changes arising in activated processes whose reaction coordinate is not known beforehand and for which the assumptions of transition state theory are invalid. The method samples the energy landscape adaptively and dets. the isoprobability surfaces for the transition: by definition the trajectories initiated anywhere on one of these surfaces has equal probability to reach first one metastable set rather than the other. Upon weighting these surfaces by the equil. probability distribution, one obtains an effective transition pathway, i.e., a tube in configuration space inside which conformational changes occur with high probability, and the assocd. rate. The method is first validated on a simple two-dimensional example; then it is applied to a model of solid-solid transformation of a condensed system.
- 88Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Efficient Exploration of Reaction Paths via a Freezing String Method. J. Chem. Phys. 2011, 135, 224108, DOI: 10.1063/1.366490188https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1SkurrN&md5=01c0f45d3455f92d1341022377717530Efficient exploration of reaction paths via a freezing string methodBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Physics (2011), 135 (22), 224108/1-224108/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The ability to efficiently locate transition states is critically important to the widespread adoption of theor. chem. techniques for their ability to accurately predict kinetic consts. Existing surface walking techniques to locate such transition states typically require an extremely good initial guess that is often beyond intuition to est. To alleviate this problem, automated techniques to locate transition state guesses have been created that take the known reactant and product endpoint structures as inputs. In this work, we present a simple method to build an approx. reaction path through a combination of interpolation and optimization. Starting from the known reactant and product structures, new nodes are interpolated inwards towards the transition state, partially optimized orthogonally to the reaction path, and then frozen before a new pair of nodes is added. The algorithm is stopped once the string ends connect. For the practical user, this method provides a quick and convenient way to generate transition state structure guesses. Tests on three reactions (cyclization of cis,cis-2,4-hexadiene, alanine dipeptide conformation transition, and ethylene dimerization in a Ni-exchanged zeolite) show that this "freezing string" method is an efficient way to identify complex transition states with significant cost savings over existing methods, particularly when high quality linear synchronous transit interpolation is employed. (c) 2011 American Institute of Physics.
- 89Behn, A.; Zimmerman, P. M.; Bell, A. T.; Head-Gordon, M. Incorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and Applications. J. Chem. Theory Comput. 2011, 7, 4019– 4025, DOI: 10.1021/ct200654u89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOqurjE&md5=f76c6427d713c0375114e0262ef0d29eIncorporating Linear Synchronous Transit Interpolation into the Growing String Method: Algorithm and ApplicationsBehn, Andrew; Zimmerman, Paul M.; Bell, Alexis T.; Head-Gordon, MartinJournal of Chemical Theory and Computation (2011), 7 (12), 4019-4025CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method is a powerful tool in the systematic study of chem. reactions with theor. methods which allows for the rapid identification of transition states connecting known reactant and product structures. However, the efficiency of this method is heavily influenced by the choice of interpolation scheme when adding new nodes to the string during optimization. In particular, the use of Cartesian coordinates with cubic spline interpolation often produces guess structures which are far from the final reaction path and require many optimization steps (and thus many energy and gradient calcns.) to yield a reasonable final structure. In this paper, we present a new method for interpolating and reparameterizing nodes within the growing string method using the linear synchronous transit method of Halgren and Lipscomb. When applied to the alanine dipeptide rearrangement and a simplified cationic alkyl ring condensation reaction, a significant speedup in terms of computational cost is achieved (30-50%).
- 90Zimmerman, P. Reliable Transition State Searches Integrated with the Growing String Method. J. Chem. Theory Comput. 2013, 9, 3043– 3050, DOI: 10.1021/ct400319w90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptFeht78%253D&md5=6f5715237172541a74de71a1781cee83Reliable Transition State Searches Integrated with the Growing String MethodZimmerman, PaulJournal of Chemical Theory and Computation (2013), 9 (7), 3043-3050CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The growing string method (GSM) is highly useful for locating reaction paths connecting two mol. intermediates. GSM has often been used in a two-step procedure to locate exact transition states (TS), where GSM creates a quality initial structure for a local TS search. This procedure and others like it, however, do not always converge to the desired transition state because the local search is sensitive to the quality of the initial guess. This article describes an integrated technique for simultaneous reaction path and exact transition state search. This is achieved by implementing an eigenvector following optimization algorithm in internal coordinates with Hessian update techniques. After partial convergence of the string, an exact saddle point search begins under the constraint that the maximized eigenmode of the TS node Hessian has significant overlap with the string tangent near the TS. Subsequent optimization maintains connectivity of the string to the TS as well as locks in the TS direction, all but eliminating the possibility that the local search leads to the wrong TS. To verify the robustness of this approach, reaction paths and TSs are found for a benchmark set of more than 100 elementary reactions.
- 91Vaucher, A. C.; Reiher, M. Minimum Energy Paths and Transition States by Curve Optimization. J. Chem. Theory Comput. 2018, 14, 3091– 3099, DOI: 10.1021/acs.jctc.8b0016991https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnsF2qtbg%253D&md5=88c0d81d005d0b913d9b75341576889dMinimum Energy Paths and Transition States by Curve OptimizationVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (6), 3091-3099CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Transition states and min. energy paths are essential to understand and predict chem. reactivity. Double-ended methods represent a std. approach for their detn. A new double-ended method that optimizes reaction paths described by curves is introduced. Unlike other methods, the approach optimizes the curve parameters rather than distinct structures along the path. With mol. paths represented as continuous curves, the optimization can benefit from the advantages of an integral-based formulation. This approach is called ReaDuct and its applicability for mol. paths parametrized by B-spline curves is demonstrated.
- 92Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and Rates. Ind. Eng. Chem. Res. 1994, 33, 790– 799, DOI: 10.1021/ie00028a00392https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXitFKnu7s%253D&md5=7cfd4d0b5f978bbea1c40e00eadcbf77Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and RatesBroadbelt, Linda J.; Stark, Scott M.; Klein, Michael T.Industrial & Engineering Chemistry Research (1994), 33 (4), 790-9CODEN: IECRED; ISSN:0888-5885.The development of an integrated system for the computer generation of kinetic models is described. Required input is the structure of the reactants, the reaction rules, and the parameters of a structure/property kinetics correlation. The algorithm transforms this information into reactant/product relationships, i.e., the reaction network, species properties, rate consts., and the FORTRAN code corresponding to the governing species' balance equations, and offers a soln. capability. Graph theory is exploited to represent the constituent atoms of a mol. to allow detn. of species' uniqueness, implement chem. reactions, and identify reaction products. Special attention was devoted to improved algorithm efficiencies, the handling of ring systems, and "on-the-fly" quantum chem. calcns. This general approach is described in using ethane and cyclohexane pyrolysis case studies. The increase in the no. of equations and no. of components for ethane pyrolysis was exponential with the carbon no. of allowed species.
- 93Broadbelt, L. J.; Stark, S. M.; Klein, M. T. Computer Generated Reaction Modelling: Decomposition and Encoding Algorithms for Determining Species Uniqueness. Comput. Chem. Eng. 1996, 20, 113– 129, DOI: 10.1016/0098-1354(94)00009-D93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1yjsL0%253D&md5=12e4ffb130284518319665befc664e09Computer generated reaction modeling: decomposition and encoding algorithms for determining species uniquenessBroadbelt, L. J.; Stark, S. M.; Klein, M. T.Computers & Chemical Engineering (1996), 20 (2), 113-29CODEN: CCENDW; ISSN:0098-1354. (Elsevier)The concept of computer generated reaction modeling was broadened through the development of a general planar graph algorithm for detn. of isomorphism. The previous capability was limited by its inability to det. the uniqueness of ring-contg. species unambiguously, restricting the application of automatic network generation to non-cyclic species or cyclic species where the ring was not involved in the chem. transformation. In this work, the systematic identification of both noncyclic and cyclic species was carried out by constructing the structurally explicit decompn. tree, an assembly of the biconnected components of the graph, from which a graph invariant unique string code was obtained by iteratively encoding and ordering the subtrees of the decompn. tree. A lexicog. comparison of the unique string code of the candidate species with the string codes of all previously generated species with the same empirical formula allowed unambiguous detn. of species uniqueness.
- 94Broadbelt, L. J.; Pfaendtner, J. Lexicography of Kinetic Modeling of Complex Reaction Networks. AIChE J. 2005, 51, 2112– 2121, DOI: 10.1002/aic.1059994https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslCnt7c%253D&md5=47e8076ea9b3fde03f4c063e018a1131Lexicography of kinetic modeling of complex reaction networksBroadbelt, Linda J.; Pfaendtner, JimAIChE Journal (2005), 51 (8), 2112-2121CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)Lexicog. of kinetic modeling of complex reaction networks is discussed.
- 95Evans, M. G.; Polanyi, M. Inertia and Driving Force of Chemical Reactions. Trans. Faraday Soc. 1938, 34, 11– 24, DOI: 10.1039/tf938340001195https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaA1cXitVWisg%253D%253D&md5=1b35420fa6bfc7cd2c1118fb7a7096ebInertia and driving force of chemical reactionsEvans, M. G.; Polanyi, M.Transactions of the Faraday Society (1938), 34 (), 11-24CODEN: TFSOA4; ISSN:0014-7672.A reaction has "inertia" if the activation energy is exothermic and has a "driving force" when the formation of new bonds lowers the activation energy. The energy surfaces of the initial and final states and the reaction paths between them as well as their relation to at. repulsions are considered.
- 96Matheu, D. M.; Dean, A. M.; Grenda, J. M.; Green, W. H. Mechanism Generation with Integrated Pressure Dependence: A New Model for Methane Pyrolysis. J. Phys. Chem. A 2003, 107, 8552– 8565, DOI: 10.1021/jp034595796https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXnsVehtLk%253D&md5=087a6a72c1556f599dbf81547530cddeMechanism Generation with Integrated Pressure Dependence: A New Model for Methane PyrolysisMatheu, David M.; Dean, Anthony M.; Grenda, Jeffrey M.; Green, William H., Jr.Journal of Physical Chemistry A (2003), 107 (41), 8552-8565CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Autocatalytic, lower-temp. (≤1100 K) methane pyrolysis has defied mechanistic explanation for almost three decades. The most recent attempt (by Dean in 1990) invoked the chem. activated addn. of an allyl radical to acetylene, leading to a cyclopentadiene/cyclopentadienyl chain-branching system that prompted the obsd. autocatalysis. However, newer, more accurate thermochem. data for the cyclopentadienyl radical render that explanation untenable. A new model for methane pyrolysis is constructed here, using a novel mechanism generation approach that automatically computes any needed rate consts. k(T,P) for chem. or thermally activated pressure-dependent reactions. The computer-generated mechanism accurately predicts the obsd. autocatalysis and concn. profiles without any adjustable parameters. Radical-forming reverse disproportionation reactions-which involve propyne, allene, and fulvene-account for at least half of the exptl. obsd. autocatalytic effect. Many of these reverse disproportionations were neglected in previous studies. The cyclopentadienyl radical is also important, but it is formed primarily by the chem. activated reaction of propargyl with acetylene. New rate ests. for unimol. ring-closure reactions of unsatd. radicals are also presented. This approach is the first to incorporate pressure-dependent reactions generally and systematically during computerized mechanism construction. It successfully identifies complex but crit. chem.-reaction pathways and autocatalytic loops missed by experienced kineticists.
- 97Gao, C. W.; Allen, J. W.; Green, W. H.; West, R. H. Reaction Mechanism Generator: Automatic Construction of Chemical Kinetic Mechanisms. Comput. Phys. Commun. 2016, 203, 212– 225, DOI: 10.1016/j.cpc.2016.02.01397https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs12kur4%253D&md5=3403c82513d617761ce38eb7de35c5c3Reaction Mechanism Generator: Automatic construction of chemical kinetic mechanismsGao, Connie W.; Allen, Joshua W.; Green, William H.; West, Richard H.Computer Physics Communications (2016), 203 (), 212-225CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier B.V.)Reaction Mechanism Generator (RMG) constructs kinetic models composed of elementary chem. reaction steps using a general understanding of how mols. react. Species thermochem. is estd. through Benson group additivity and reaction rate coeffs. are estd. using a database of known rate rules and reaction templates. At its core, RMG relies on two fundamental data structures: graphs and trees. Graphs are used to represent chem. structures, and trees are used to represent thermodn. and kinetic data. Models are generated using a rate-based algorithm which excludes species from the model based on reaction fluxes. RMG can generate reaction mechanisms for species involving carbon, hydrogen, oxygen, sulfur, and nitrogen. It also has capabilities for estg. transport and solvation properties, and it automatically computes pressure-dependent rate coeffs. and identifies chem.-activated reaction paths. RMG is an object-oriented program written in Python, which provides a stable, robust programming architecture for developing an extensible and modular code base with a large suite of unit tests. Computationally intensive functions are cythonized for speed improvements.
- 98Harper, M. R.; Van Geem, K. M.; Pyl, S. P.; Marin, G. B.; Green, W. H. Comprehensive Reaction Mechanism for N-Butanol Pyrolysis and Combustion. Combust. Flame 2011, 158, 16– 41, DOI: 10.1016/j.combustflame.2010.06.00298https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVWht7zI&md5=73235ccdbc0fdce97f3c1a8b423bc3bbComprehensive reaction mechanism for n-butanol pyrolysis and combustionHarper, Michael R.; Van Geem, Kevin M.; Pyl, Steven P.; Marin, Guy B.; Green, William H.Combustion and Flame (2011), 158 (1), 16-41CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)A detailed reaction mechanism for n-butanol, consisting of 263 species and 3381 reactions, has been generated using the open-source software package, Reaction Mechanism Generator (RMG). The mechanism is tested against recently published data - jet-stirred reactor mole fraction profiles, opposed-flow diffusion flame mole fraction profiles, autoignition delay times, and doped methane diffusion flame mole fraction profiles - and newly acquired n-butanol pyrolysis expts. with very encouraging results. The chem. of butanal is also validated against autoignition delay times obtained in shock tube expts. A flux and sensitivity anal. for each simulated dataset is discussed and reveals important reactions where more accurate rate const. ests. were required. New rate const. expressions were computed using quantum chem. and transition state theory calcns. Furthermore, in addn. to comparing the proposed model with the eight datasets, the model is also compared with recently published n-butanol models for three of the datasets. Key differences between the proposed model and the published models are discussed.
- 99van Geem, K. M.; Reyniers, M.-F.; Marin, G. B.; Song, J.; Green, W. H.; Matheu, D. M. Automatic Reaction Network Generation Using RMG for Steam Cracking of N-hexane. AIChE J. 2006, 52, 718– 730, DOI: 10.1002/aic.1065599https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xht1Ogu7s%253D&md5=d20f9949dd0516d2ef7b2bba4d919fa5Automatic reaction network generation using RMG for steam cracking of n-hexaneVan Geem, Kevin M.; Reyniers, Marie-Francoise; Marin, Guy B.; Song, Jing; Green, William H.; Matheu, David M.AIChE Journal (2006), 52 (2), 718-730CODEN: AICEAC; ISSN:0001-1541. (John Wiley & Sons, Inc.)A new reaction mechanism generator RMG is used to automatically construct a pressure dependent kinetic model for the steam cracking of n-hexane. Comparison between simulated and pilot plant data shows that RMG is able to generate detailed reaction networks that accurately predict the conversion and the yields of the major products although none of the kinetic parameters are fit to the expts. RMG generates reaction networks based on minimal assumptions, making it possible to test commonly used assumptions such as the μ-hypothesis and the quasi steady-state approxn. (QSSA) for μ-radicals, traditionally used in steam cracking,1,2 as well as in pyrolysis. The RMG-reaction network for n-hexane confirms that no bimol. reactions of heavy radical species are important at the examd. conditions (COT: 953 K - 1090 K; COP: 0.20 MPa -0.24 MPa; <80% conversion), and that the QSSA for the group of μ-radicals leads to negligible errors. RMG also offers the possibility to est. the error introduced by neglecting the pressure dependence of most of the reactions. In the case studied, this frequently made (but seldom tested) approxn. appears to be justified.
- 100Petway, S. V.; Ismail, H.; Green, W. H.; Estupiñán, E. G.; Jusinski, L. E.; Taatjes, C. A. Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl Radical. J. Phys. Chem. A 2007, 111, 3891– 3900, DOI: 10.1021/jp0668549100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXkt1Ortrk%253D&md5=65ea9d850eea1b016f8f57d241479b04Measurements and Automated Mechanism Generation Modeling of OH Production in Photolytically Initiated Oxidation of the Neopentyl RadicalPetway, Sarah V.; Ismail, Huzeifa; Green, William H.; Estupinan, Edgar G.; Jusinski, Leonard E.; Taatjes, Craig A.Journal of Physical Chemistry A (2007), 111 (19), 3891-3900CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Prodn. of OH in the reaction of the neopentyl radical with O2 has been measured by a laser photolysis/cw absorption method for various pressures and oxygen concns. at 673, 700, and 725 K. The MIT Reaction Mechanism Generator (RMG) was used to automatically generate a model for this system, and the predicted OH concn. profiles are compared to present and literature exptl. results. Several reactions significantly affect the OH profile. The exptl. data provide useful constraints on the rate coeff. for the formally direct chem. activation reaction of neopentyl radical with O2 to form OH (CH3)3CCH2 + O2 → OH + 3,3-dimethyloxetane (Rxn 1) At 673 K and 60 Torr, log k1 (cm3 mol.-1 s-1) = -13.7 ± 0.5. Abs. absorbance measurements on OH and I indicate that the branching ratio for R + O2 to OH is about 0.03 under these conditions. The data suggest that the ab initio neopentyl + O2 potential energy surface of Sun and Bozzelli is accurate to within 2 kcal mol-1.
- 101Hansen, N.; Merchant, S. S.; Harper, M. R.; Green, W. H. The Predictive Capability of an Automatically Generated Combustion Chemistry Mechanism: Chemical Structures of Premixed Iso-Butanol Flames. Combust. Flame 2013, 160, 2343– 2351, DOI: 10.1016/j.combustflame.2013.05.013101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXpsV2ksbY%253D&md5=e7e16e09c9c3b50328ce0686d91b3b37The predictive capability of an automatically generated combustion chemistry mechanism: Chemical structures of premixed iso-butanol flamesHansen, Nils; Merchant, Shamel S.; Harper, Michael R.; Green, William H.Combustion and Flame (2013), 160 (11), 2343-2351CODEN: CBFMAO; ISSN:0010-2180. (Elsevier B.V.)The chem. compns. of four low-pressure premixed flames of iso-butanol are investigated with an emphasis on assessing the predictive capabilities of an automatically generated combustion chem. model. This kinetic model had been extensively tested against earlier exptl. data [S.S. Merchant, E.F. Zanoelo, R.L. Speth, M.R. Harper, K.M. Van Geem, W.H. Green, Combust. Flame (2013), http://dx.doi.org/10.1016/j.combustflame.2013.04.023.] and also shows impressive capabilities for predicting the new flame data presented here. The new set of data consists of isomer-resolved mole fraction profiles for more than 40 species in each of the four flames and provides a comprehensive benchmark for testing of any combustion chem. model for iso-butanol. Isomer-specificity is achieved by analyzing flames, which are burner-stabilized at equivalence ratios of .vphi. = 1.0-1.5 and at pressures between 15-30 Torr, with mol.-beam mass spectrometry and single-photon ionization by tunable vacuum-UV synchrotron radiation. Predictions of the C2H4O, C3H6O, and C4H8O enol-aldehyde-ketone isomers are improved compared to the earlier work by Hansen et al. [N. Hansen, M. R. Harper, W. H. Green, Phys. Chem. Chem. Phys. 13 (2011) 20262-20274] on similar n-butanol flames. A reaction path anal. identifies prominent fuel-consumption and oxidn. sequences. Almost all of the species mole fraction data reported here are predicted within the measurement uncertainties of a factor of two to three. Some significant differences with previous published models are highlighted.
- 102Slakman, B. L.; Simka, H.; Reddy, H.; West, R. H. Extending Reaction Mechanism Generator to Silicon Hydride Chemistry. Ind. Eng. Chem. Res. 2016, 55, 12507– 12515, DOI: 10.1021/acs.iecr.6b02402102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslOhsr%252FI&md5=51d944ea4978704bfbe0e0f68e7e0ca0Extending Reaction Mechanism Generator to Silicon Hydride ChemistrySlakman, Belinda L.; Simka, Harsono; Reddy, Harinath; West, Richard H.Industrial & Engineering Chemistry Research (2016), 55 (49), 12507-12515CODEN: IECRED; ISSN:0888-5885. (American Chemical Society)Understanding the gas-phase chem. of Si hydrides is the 1st step to building a realistic kinetic model for chem. vapor deposition (CVD). Functionality for thermodn. and kinetic data estn. of Si hydrides was added to the open-source software Reaction Mechanism Generator (RMG). Using the updated RMG, a detailed kinetic model was built for SiH4 thermal decompn. The generated model was used to perform reactor simulations at various process conditions for comparison to prior SiH4 decompn. expts. in a flow tube. Results show that the RMG-generated model can reasonably replicate exptl. results for SiH4 concn. profiles at different temps. and residence times. While the effect of changing initial SiH4 concn. is not captured, a 1st pass sensitivity anal. reveals that reasonable errors in reaction rates could contribute to the discrepancy.
- 103Seyedzadeh Khanshan, F.; West, R. H. Developing Detailed Kinetic Models of Syngas Production from Bio-Oil Gasification Using Reaction Mechanism Generator (RMG). Fuel 2016, 163, 25– 33, DOI: 10.1016/j.fuel.2015.09.031103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFersbjJ&md5=40a7d6183fcf086f287431148682cde2Developing detailed kinetic models of syngas production from bio-oil gasification using Reaction Mechanism Generator (RMG)Seyedzadeh Khanshan, Fariba; West, Richard H.Fuel (2016), 163 (), 25-33CODEN: FUELAC; ISSN:0016-2361. (Elsevier Ltd.)Detailed kinetic models for the conversion of bio-oil to syngas through gasification were developed automatically using the open source software package Reaction Mechanism Generator (RMG). The influences of process operating conditions and of RMG parameters on the performance of models were investigated. Both temp. and pressure alter the product yields, although including pressure-dependent (chem. activated and fall-off) kinetics have minimal impact on these predictions. The model size is important, although currently constrained by available RAM, motivating development of improved memory-management algorithms in RMG. To validate the RMG-built mechanisms, simulations performed with Cantera were compared with exptl. data from the literature. Agreements and disagreements between RMG-built models and literature show that the automated mechanism generation approach is promising, but reveal some families of reactions involving heteroat. cycles that require improved ests. for bio-mass derived fuels. Research in this area would be greatly helped by more quant. exptl. data, ideally showing intermediate species profiles. These findings motivate extra studies and guide further RMG development.
- 104Han, K.; Green, W. H.; West, R. H. On-the-Fly Pruning for Rate-Based Reaction Mechanism Generation. Comput. Chem. Eng. 2017, 100, 1– 8, DOI: 10.1016/j.compchemeng.2017.01.003104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVGgtLw%253D&md5=b48df5ab6c5e4d5f93447f5a562f8270On-the-fly pruning for rate-based reaction mechanism generationHan, Kehang; Green, William H.; West, Richard H.Computers & Chemical Engineering (2017), 100 (), 1-8CODEN: CCENDW; ISSN:0098-1354. (Elsevier B.V.)The no. of possible side reactions and byproduct species grows very rapidly with the size of a chem. mechanism. A memory-efficient algorithm for automated mechanism generation is presented for coping with this combinatorial complexity. The algorithm selects normalized flux as a metric to identify unimportant species during model generation and prunes them with their reactions, without any loss of accuracy. The new algorithm reduces memory requirements for building kinetic models with 200-300 species by about a factor of 4, or for fixed computer hardware makes it possible to create models including about twice as many species as was previously possible. The increased capability opens the possibility of discovering unexplored reaction networks and modeling more complicated reacting systems.
- 105Dana, A. G.; Buesser, B.; Merchant, S. S.; Green, W. H. Automated Reaction Mechanism Generation Including Nitrogen as a Heteroatom. Int. J. Chem. Kinet. 2018, 50, 243– 258, DOI: 10.1002/kin.21154105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOqtbo%253D&md5=5ce0d70f40dea1ec2bea8cfac28998b0Automated Reaction Mechanism Generation Including Nitrogen as a HeteroatomDana, Alon Grinberg; Buesser, Beat; Merchant, Shamel S.; Green, William H.International Journal of Chemical Kinetics (2018), 50 (4), 243-258CODEN: IJCKBO; ISSN:0538-8066. (John Wiley & Sons, Inc.)The open source rate-based Reaction Mechanism Generator (RMG) software and its thermochem. and kinetics databases were extended to include nitrogen as a heteroatom. Specific changes to RMG and the mining of thermochem. and reaction kinetics data are discussed. This new version of RMG has been tested by generating a detailed pyrolysis and oxidn. model for ethylamine (EA, CH3CH2NH2) at ∼1400 K and ∼2 bar, and comparing it to recent shock tube studies. Validation of the reaction network with recent exptl. data showed that the generated model successfully reproduced the obsd. species as well as ignition delay measurements. During pyrolysis, EA initially decomps. via a C-C bond scission, and the CH2NH2 product subsequently produces the first H radicals in this system via β-scission. As the concn. of H increases, the major EA consuming reaction becomes H abstraction at the α-site by H radicals, leading to a chain reaction since its product generates more H radicals. During oxidn., the dominant N2-producing route is mediated by NO and N2O. The observables were found to be relatively sensitive to the C-C and C-N EA bond scission reactions as well as to the thermodn. values of EA; thermodn. data for EA were computed at the CBS-QB3 level and reported herein. This work demonstrates the ability of RMG to construct adequate kinetic models for nitrogenous species and discusses the pyrolysis and oxidn. mechanisms of EA.
- 106Grambow, C. A.; Jamal, A.; Li, Y.-P.; Green, W. H.; Zádor, J.; Suleimanov, Y. V. Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods. J. Am. Chem. Soc. 2018, 140, 1035– 1048, DOI: 10.1021/jacs.7b11009106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitVaksr%252FN&md5=cc0ce7340d7035db8729dd9cc71478d5Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery MethodsGrambow, Colin A.; Jamal, Adeel; Li, Yi-Pei; Green, William H.; Zador, Judit; Suleimanov, Yury V.Journal of the American Chemical Society (2018), 140 (3), 1035-1048CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Ketohydroperoxides are important in liq.-phase autoxidn. and in gas-phase partial oxidn. and pre-ignition chem., but because of their low concn., instability, and various anal. chem. limitations, it has been challenging to exptl. det. their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimol. reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of d. functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The present joint approach significantly outperforms previous manual and automated transition-state searches - 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chem. reactions involve promising new chem. that may be relevant in atm. and combustion systems. Our study highlights the complexity of chem. space exploration and the advantage of combined application of several approaches. Overall, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).
- 107Suleimanov, Y. V.; Green, W. H. Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization Methods. J. Chem. Theory Comput. 2015, 11, 4248, DOI: 10.1021/acs.jctc.5b00407107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1Srsb7I&md5=d430c76d756be29d6c52befc113e6400Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization MethodsSuleimanov, Yury V.; Green, William H.Journal of Chemical Theory and Computation (2015), 11 (9), 4248-4259CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We present a simple protocol which allows fully automated discovery of elementary chem. reaction steps using in cooperation double- and single-ended transition-state optimization algorithms - the freezing string and Berny optimization methods, resp. To demonstrate the utility of the proposed approach, the reactivity of several single-mol. systems of combustion and atm. chem. importance is investigated. The proposed algorithm allowed us to detect without any human intervention not only "known" reaction pathways, manually detected in the previous studies, but also new, previously "unknown", reaction pathways which involve significant atom rearrangements. We believe that applying such a systematic approach to elementary reaction path finding will greatly accelerate the discovery of new chem. and will lead to more accurate computer simulations of various chem. processes.
- 108Schlegel, H. B. Optimization of Equilibrium Geometries and Transition Structures. J. Comput. Chem. 1982, 3, 214– 218, DOI: 10.1002/jcc.540030212108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL38XktFajtrY%253D&md5=81448fcccb0620eff4b6754171e84f70Optimization of equilibrium geometries and transition structuresSchlegel, H. BernhardJournal of Computational Chemistry (1982), 3 (2), 214-18CODEN: JCCHDD; ISSN:0192-8651.A modified conjugate gradient algorithm for geometry optimization is outlined for use with ab initio MO methods. Since the computation time for anal. energy gradients is approx. the same as for the energy, the optimization algorithm evaluates and utilizes the gradients each time the energy is computed. The second deriv. matrix, rather than its inverse, is updated employing the gradients. At each step, a one-dimensional minimization using a quartic polynomial is carried out, followed by an n-dimensional search using the second deriv. matrix. By suitably controlling the no. of neg. eigenvalues of the second deriv. matrix, the algorithm can also be used to locate transition structures. Representative timeing data for optimizations of equil. geometries and transition structures are reported for ab initio SCF-MO calcns.
- 109Schlegel, H. B. Estimating the Hessian for Gradient-Type Geometry Optimizations. Theoret. Chim. Acta 1984, 66, 333– 340, DOI: 10.1007/BF00554788There is no corresponding record for this reference.
- 110Peng, C.; Ayala, P. Y.; Schlegel, H. B.; Frisch, M. J. Using Redundant Internal Coordinates to Optimize Equilibrium Geometries and Transition States. J. Comput. Chem. 1996, 17, 49– 56, DOI: 10.1002/(SICI)1096-987X(19960115)17:1<49::AID-JCC5>3.0.CO;2-0110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XpvFSi&md5=330450a8e3f31abc94db9435cfe23935Using redundant internal coordinates to optimize equilibrium geometries and transition statesPeng, Chunyang; Ayala, Philippe; Schlegel, H. Bernhard; Frisch, Michael J.Journal of Computational Chemistry (1996), 17 (1), 49-56CODEN: JCCHDD; ISSN:0192-8651. (Wiley)A redundant internal coordinate system for optimizing mol. geometries is constructed from all bonds, all valence angles between bonded atoms, and all dihedral angles between bonded atoms. Redundancies are removed by using the generalized inverse of the G matrix; constraints can be added by using an appropriate projects. For minimizations, redundant internal coordinates provide substantial improvements in optimization efficiency over Cartesian and nonredundant internal coordinates, esp. for flexible and polycyclic systems. Transition structure searches are also improved when redundant coordinates are used and when the initial steps are guided by the quadratic synchronous transit approach.
- 111Bhoorasingh, P. L.; West, R. H. Transition State Geometry Prediction Using Molecular Group Contributions. Phys. Chem. Chem. Phys. 2015, 17, 32173– 32182, DOI: 10.1039/C5CP04706D111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFKhtb3P&md5=16e7f411e54e0417dfd07bbf66ac66b2Transition state geometry prediction using molecular group contributionsBhoorasingh, Pierre L.; West, Richard H.Physical Chemistry Chemical Physics (2015), 17 (48), 32173-32182CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Detailed kinetic models to aid the understanding of complex chem. systems require many thousands of reaction rate coeffs., most of which are estd., some quite approx. and with unknown uncertainties. This motivates the development of high-throughput methods to det. rate coeffs. via transition state theory calcns., which requires the automatic prediction of transition state (TS) geometries. We demonstrate a novel approach to predict TS geometries using a group-additive method. Distances between reactive atoms at the TS are estd. using mol. group values, with the 3D geometry of the TS being constructed by distance geometry. The est. is then optimized using electronic structure theory and validated using intrinsic reaction coordinate calcns., completing the fully automatic algorithm to locate TS geometries. The methods were tested using a diisopropyl ketone combustion model contg. 1393 hydrogen abstraction reactions, of which transition states were found for 907 over two iterations of the algorithm. With sufficient training data, mol. group contributions were shown to successfully predict the reaction center distances of transition states with root-mean-squared errors of only 0.04 Å.
- 112Rappoport, D.; Galvin, C. J.; Zubarev, D. Y.; Aspuru-Guzik, A. Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry. J. Chem. Theory Comput. 2014, 10, 897– 907, DOI: 10.1021/ct401004r112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVOqurY%253D&md5=64f81a54964e1e07a08421b61e45f495Complex Chemical Reaction Networks from Heuristics-Aided Quantum ChemistryRappoport, Dmitrij; Galvin, Cooper J.; Zubarev, Dmitry Yu.; Aspuru-Guzik, AlanJournal of Chemical Theory and Computation (2014), 10 (3), 897-907CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)While structures and reactivities of many small mols. can be computed efficiently and accurately using quantum chem. methods, heuristic approaches remain essential for modeling complex structures and large-scale chem. systems. Here, we present a heuristics-aided quantum chem. methodol. applicable to complex chem. reaction networks such as those arising in cell metab. and prebiotic chem. Chem. heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chem. structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chem. methodol. to the formose reaction reproduces the exptl. obsd. reaction products, major reaction pathways, and autocatalytic cycles.
- 113Zubarev, D. Y.; Rappoport, D.; Aspuru-Guzik, A. Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle. Sci. Rep. 2015, 5, 8009, DOI: 10.1038/srep08009113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXotlagsrs%253D&md5=76b8b2e61796a6a68b76dd84a9e3b45dUncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid CycleZubarev, Dmitry Yu; Rappoport, Dmitrij; Aspuru-Guzik, AlanScientific Reports (2015), 5 (), 8009/1-8009/7CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)We consider the hypothesis of the primordial nature of the non-enzymic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chem. transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.
- 114Rappoport, D.; Aspuru-Guzik, A. Predicting Feasible Organic Reaction Pathways Using Heuristically Aided Quantum Chemistry. ChemRxiv Preprint 2018, DOI: 10.26434/chemrxiv.6649565.v1There is no corresponding record for this reference.
- 115Butlerow, A. Bildung einer zuckerartigen Substanz durch Synthese. Justus Liebigs Ann. Chem. 1861, 120, 295– 298, DOI: 10.1002/jlac.18611200308There is no corresponding record for this reference.
- 116Levy, D. E. Arrow-Pushing in Organic Chemistry: An Easy Approach to Understanding Reaction Mechanisms, 2nd ed.; Wiley, 2017.There is no corresponding record for this reference.
- 117Kim, Y.; Woo Kim, J.; Kim, Z.; Youn Kim, W. Efficient Prediction of Reaction Paths through Molecular Graph and Reaction Network Analysis. Chem. Sci. 2018, 9, 825– 835, DOI: 10.1039/C7SC03628K117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFGnsbjI&md5=71d81e16d0ac1ee7164da8f664e8dcbbEfficient prediction of reaction paths through molecular graph and reaction network analysisKim, Yeonjoon; Kim, Jin Woo; Kim, Zeehyo; Kim, Woo YounChemical Science (2018), 9 (4), 825-835CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)Despite remarkable advances in computational chem., prediction of reaction mechanisms is still challenging, because investigating all possible reaction pathways is computationally prohibitive due to the high complexity of chem. space. A feasible strategy for efficient prediction is to utilize chem. heuristics. Here, we propose a novel approach to rapidly search reaction paths in a fully automated fashion by combining chem. theory and heuristics. A key idea of our method is to ext. a minimal reaction network composed of only favorable reaction pathways from the complex chem. space through mol. graph and reaction network anal. This can be done very efficiently by exploring the routes connecting reactants and products with min. dissocn. and formation of bonds. Finally, the resulting minimal network is subjected to quantum chem. calcns. to det. kinetically the most favorable reaction path at the predictable accuracy. As example studies, our method was able to successfully find the accepted mechanisms of Claisen ester condensation and cobalt-catalyzed hydroformylation reactions.
- 118Zimmerman, P. M. Automated Discovery of Chemically Reasonable Elementary Reaction Steps. J. Comput. Chem. 2013, 34, 1385– 1392, DOI: 10.1002/jcc.23271118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktFWhtb4%253D&md5=443c5c1be4f67d956c120a64a77ee82dAutomated discovery of chemically reasonable elementary reaction stepsZimmerman, Paul M.Journal of Computational Chemistry (2013), 34 (16), 1385-1392CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Due to the significant human effort and chem. intuition required to locate chem. reaction pathways with quantum chem. modeling, only a small subspace of possible reactions is usually studied for any given system. Herein, a systematic approach is proposed for locating reaction paths that bypasses the required human effort and expands the reactive search space, all while maintaining low computational cost. To achieve this, a range of intermediates are generated that represent potential single elementary steps away from a starting structure. These structures are then screened to identify those that are thermodynamically accessible, and then feasible reaction paths to the remaining structures are located. This strategy for elementary reaction path finding is independent of atomistic model whenever bond breaking and forming are properly described. The approach is demonstrated to work well for upper main group elements, but this limitation can easily be surpassed. Further extension will allow discovery of multistep reaction mechanisms in a single computation. The method is highly parallel, allowing for effective use of modern large-scale computational clusters. © 2013 Wiley Periodicals, Inc.
- 119Zimmerman, P. M. Navigating Molecular Space for Reaction Mechanisms: An Efficient, Automated Procedure. Mol. Simul. 2015, 41, 43– 54, DOI: 10.1080/08927022.2014.894999119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFait7k%253D&md5=4e996b3b2f43c78843468df3e622b79aNavigating molecular space for reaction mechanisms: an efficient, automated procedureZimmerman, Paul M.Molecular Simulation (2015), 41 (1-3), 43-54CODEN: MOSIEA; ISSN:0892-7022. (Taylor & Francis Ltd.)A review; mechanism is a core chem. concept that has vital implications for reaction rate, efficiency and selectivity. The discovery of mechanism is not easy due to the great diversity of possible chem. rearrangements in even relatively simple systems. For this reason, mechanisms involving bond breaking and forming are usually proposed via chem. intuition - which limits the scope of considered possibilities - and these hypotheses are then tested using simulation or expt. This article discusses an automated simulation strategy for investigating multiple elementary step reaction mechanisms in chem. systems. The method starts from a single input structure and seeks out nearby intermediates, optimizes the proposed structures and then dets. the kinetic viability of each elementary step. The kinetically accessible intermediates are catalogued and new searches are performed on each unique structure. This process is repeated for an arbitrary no. of steps without human intervention, and massively parallel computation enables fast searches in chem. space. Importantly, this strategy can be empirically shown to lead to a finite no. of accessible structures, not a combinatorial explosion of intermediates. Therefore, the method should be able to predict multi-step reaction pathways in many interesting chem. systems. Demonstrations on org. reactions and a hydrogen storage material, ammonia borane, show that the herein proposed strategy can uncover complex reactivity without relying on existing chem. intuition.
- 120Zimmerman, P. M. Growing String Method with Interpolation and Optimization in Internal Coordinates: Method and Examples. J. Chem. Phys. 2013, 138, 184102, DOI: 10.1063/1.4804162120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsV2isLg%253D&md5=e315e6f2a3e4e1bf65e743d1ee3863b5Growing string method with interpolation and optimization in internal coordinates: Method and examplesZimmerman, Paul M.Journal of Chemical Physics (2013), 138 (18), 184102/1-184102/10CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)The growing string method (GSM) has proven esp. useful for locating chem. reaction paths at low computational cost. While many string methods use Cartesian coordinates, these methods can be substantially improved by changes in the coordinate system used for interpolation and optimization steps. The quality of the interpolation scheme is esp. important because it dets. how close the initial path is to the optimized reaction path, and this strongly affects the rate of convergence. In this article, a detailed description of the generation of internal coordinates (ICs) suitable for use in GSM as reactive tangents and in string optimization is given. Convergence of reaction paths is smooth because the IC tangent and orthogonal directions are better representations of chem. bonding compared to Cartesian coordinates. This is not only important quant. for reducing computational cost but also allows reaction paths to be described with smoothly varying chem. relevant coordinates. Benchmark computations with challenging reactions are compared to previous versions of GSM and show significant speedups. Finally, a climbing image scheme is included to improve the quality of the transition state approxn., ensuring high reliability of the method. (c) 2013 American Institute of Physics.
- 121Zimmerman, P. M. Single-Ended Transition State Finding with the Growing String Method. J. Comput. Chem. 2015, 36, 601– 611, DOI: 10.1002/jcc.23833121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXltVKlsQ%253D%253D&md5=4b3087ccfd79ea3fba13820a2be013e3Single-ended transition state finding with the growing string methodZimmerman, Paul M.Journal of Computational Chemistry (2015), 36 (9), 601-611CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Reaction path finding and transition state (TS) searching are important tasks in computational chem. Methods that seek to optimize an evenly distributed set of structures to represent a chem. reaction path are known as double-ended string methods. Such methods can be highly reliable because the endpoints of the string are fixed, which effectively lowers the dimensionality of the reaction path search. String methods, however, require that the reactant and product structures are known beforehand, which limits their ability for systematic exploration of reactive steps. In this article, a single-ended growing string method (GSM) is introduced which allows for reaction path searches starting from a single structure. The method works by sequentially adding nodes along coordinates that drive bonds, angles, and/or torsions to a desired reactive outcome. After the string is grown and an approx. reaction path through the TS is found, string optimization commences and the exact TS is located along with the reaction path. Fast convergence of the string is achieved through use of internal coordinates and eigenvector optimization schemes combined with Hessian ests. Comparison to the double-ended GSM shows that single-ended method can be even more computationally efficient than the already rapid double-ended method. Examples, including transition metal reactivity and a systematic, automated search for unknown reactivity, demonstrate the efficacy of the new method. This automated reaction search is able to find 165 reaction paths from 333 searches for the reaction of NH3BH3 and (LiH)4, all without guidance from user intuition. © 2015 Wiley Periodicals, Inc.
- 122Jafari, M.; Zimmerman, P. M. Reliable and Efficient Reaction Path and Transition State Finding for Surface Reactions with the Growing String Method. J. Comput. Chem. 2017, 38, 645– 658, DOI: 10.1002/jcc.24720122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslSju74%253D&md5=a8441a251705eefd13a4c844ad88da74Reliable and efficient reaction path and transition state finding for surface reactions with the growing string methodJafari, Mina; Zimmerman, Paul M.Journal of Computational Chemistry (2017), 38 (10), 645-658CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)The computational challenge of fast and reliable transition state and reaction path optimization requires new methodol. strategies to maintain low cost, high accuracy, and systematic searching capabilities. The growing string method using internal coordinates has proven to be highly effective for the study of mol., gas phase reactions, but difficulties in choosing a suitable coordinate system for periodic systems has prevented its use for surface chem. New developments are therefore needed, and presented herein, to handle surface reactions which include atoms with large coordination nos. that cannot be treated using std. internal coordinates. The double-ended and single-ended growing string methods are implemented using a hybrid coordinate system, then benchmarked for a test set of 43 elementary reactions occurring on surfaces. These results show that the growing string method is at least 45% faster than the widely used climbing image-nudged elastic band method, which also fails to converge in several of the test cases. Addnl., the surface growing string method has a unique single-ended search method which can move outward from an initial structure to find the intermediates, transition states, and reaction paths simultaneously. This powerful explorative feature of single ended-growing string method is demonstrated to uncover, for the first time, the mechanism for at. layer deposition of TiN on Cu(111) surface. This reaction is found to proceed through multiple hydrogen-transfer and ligand-exchange events, while formation of H-bonds stabilizes intermediates of the reaction. Purging gaseous products out of the reaction environment is the driving force for these reactions. © 2017 Wiley Periodicals, Inc.
- 123Nett, A. J.; Zhao, W.; Zimmerman, P. M.; Montgomery, J. Highly Active Nickel Catalysts for C–H Functionalization Identified through Analysis of Off-Cycle Intermediates. J. Am. Chem. Soc. 2015, 137, 7636– 7639, DOI: 10.1021/jacs.5b04548123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVansLzJ&md5=a505b5a761d3a525a26dbb20f9b815e9Highly Active Nickel Catalysts for C-H Functionalization Identified through Analysis of Off-Cycle IntermediatesNett, Alex J.; Zhao, Wanxiang; Zimmerman, Paul M.; Montgomery, JohnJournal of the American Chemical Society (2015), 137 (24), 7636-7639CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An inhibitory role of 1,5-cyclooctadiene (COD) in nickel-catalyzed C-H functionalization processes was identified and studied. The bound COD participates in C-H activation by capturing the hydride, leading to a stable off-cycle π-allyl complex that greatly diminished overall catalytic efficiency. Computational studies elucidated the origin of the effect and enabled identification of a 1,5-hexadiene-derived pre-catalyst that avoids the off-cycle intermediate and provides catalytic efficiencies that are superior to those of catalysts derived from Ni(COD)2.
- 124Li, M. W.; Pendleton, I. M.; Nett, A. J.; Zimmerman, P. M. Mechanism for Forming B,C,N,O Rings from NH3BH3and vCO2ia Reaction Discovery Computations. J. Phys. Chem. A 2016, 120, 1135– 1144, DOI: 10.1021/acs.jpca.5b11156There is no corresponding record for this reference.
- 125Pendleton, I. M.; Pérez-Temprano, M. H.; Sanford, M. S.; Zimmerman, P. M. Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)–N Bond-Forming Reductive Elimination from Palladium(IV). J. Am. Chem. Soc. 2016, 138, 6049– 6060, DOI: 10.1021/jacs.6b02714125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtF2murk%253D&md5=f739ebd816c70d6b9930b82153ca7aa7Experimental and Computational Assessment of Reactivity and Mechanism in C(sp3)-N Bond-Forming Reductive Elimination from Palladium(IV)Pendleton, Ian M.; Perez-Temprano, Monica H.; Sanford, Melanie S.; Zimmerman, Paul M.Journal of the American Chemical Society (2016), 138 (18), 6049-6060CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)This report describes a combined exptl. and computational investigation of the mechanism of C(sp3)-N bond-forming reductive elimination from sulfonamide-ligated PdIV complexes. After an initial exptl. assessment of reactivity, we used ZStruct, a computational combinatorial reaction finding method, to analyze a large no. of multistep mechanisms for this process. This study reveals two facile isomerization pathways connecting the exptl. obsd. PdIV isomers, along with two competing SN2 pathways for C(sp3)-N coupling. One of these pathways involves an unanticipated oxygen-nitrogen exchange of the sulfonamide ligand prior to an inner-sphere SN2-type reductive elimination. The calcd. ΔG⧺ values for isomerization and reductive elimination with a series of sulfonamide derivs. are in good agreement with exptl. data. Furthermore, the simulations predict relative reaction rates with different sulfonamides, which is successful only after considering competition between the proposed operating mechanisms. Overall, this work shows that the combination of exptl. studies and new computational tools can provide fundamental mechanistic insights into complex organometallic reaction pathways.
- 126Zhao, Y.; Nett, A. J.; McNeil, A. J.; Zimmerman, P. M. Computational Mechanism for Initiation and Growth of Poly(3-Hexylthiophene) Using Palladium N-Heterocyclic Carbene Precatalysts. Macromolecules 2016, 49, 7632– 7641, DOI: 10.1021/acs.macromol.6b01648There is no corresponding record for this reference.
- 127Dewyer, A. L.; Zimmerman, P. M. Finding Reaction Mechanisms, Intuitive or Otherwise. Org. Biomol. Chem. 2017, 15, 501– 504, DOI: 10.1039/C6OB02183B127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVyjtbjJ&md5=1f70486f3755a036f7a878bbf98bc52bFinding reaction mechanisms, intuitive or otherwiseDewyer, Amanda L.; Zimmerman, Paul M.Organic & Biomolecular Chemistry (2017), 15 (3), 501-504CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)Chem. reaction mechanisms have been frequently studied using computational simulations, but these tools have been primarily effective at examg. reaction paths within the scope of chem. intuition. To det. reaction mechanisms that were not already preconceived by chemists, nonstandard simulation tools are required. This perspective introduces new methods developed by the Zimmerman group that are designed to uncover sequences of elementary steps, from first principles and without substantial human guidance. Results from the areas of organo catalysis and transition metal catalysis indicate that new frontiers of knowledge will be gained through continued development and application of reaction discovery simulation techniques.
- 128Ludwig, J. R.; Zimmerman, P. M.; Gianino, J. B.; Schindler, C. S. Iron(III)-Catalysed Carbonyl–Olefin Metathesis. Nature 2016, 533, 374– 379, DOI: 10.1038/nature17432128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmvVGntrY%253D&md5=4763c79022c8121eef0dc857214954dbIron(III)-catalysed carbonyl-olefin metathesisLudwig, Jacob R.; Zimmerman, Paul M.; Gianino, Joseph B.; Schindler, Corinna S.Nature (London, United Kingdom) (2016), 533 (7603), 374-379CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The olefin metathesis reaction of two unsatd. substrates is one of the most powerful carbon-carbon-bond-forming reactions in org. chem. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of mols. relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
- 129Smith, M. L.; Leone, A. K.; Zimmerman, P. M.; McNeil, A. J. Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole Derivatives. ACS Macro Lett. 2016, 5, 1411– 1415, DOI: 10.1021/acsmacrolett.6b00886129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVejsLbP&md5=ecff32183eb4d751c490869b57211ab3Impact of Preferential π-Binding in Catalyst-Transfer Polycondensation of Thiazole DerivativesSmith, Mitchell L.; Leone, Amanda K.; Zimmerman, Paul M.; McNeil, Anne J.ACS Macro Letters (2016), 5 (12), 1411-1415CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)Polymg. electron-deficient arenes in a controlled, chain-growth fashion remains a significant challenge despite a decade of research on catalyst-transfer polycondensation. The prevailing hypothesis is that the chain-growth mechanism stalls at a strongly assocd. metal-polymer π-complex, preventing catalyst turnover. To evaluate this hypothesis, we performed mechanistic studies using thiazole derivs. and identified approaches to improve their chain-growth polymn. These studies revealed a surprisingly high barrier for chain-walking toward the reactive C-X bond. In addn., a competitive pathway involving chain-transfer to monomer was identified. This pathway is facilitated by ancillary ligand dissocn. and N-coordination to the incoming monomer. We found that this chain-transfer pathway can be attenuated by using a rigid ancillary ligand, leading to an improved polymn. Combined, these studies provide mechanistic insight into the challenges assocd. with electron-deficient monomers and ways to improve their living, chain-growth polymn. Our mechanistic studies also revealed an unexpected radical anion-mediated oligomerization in the absence of catalyst, and a surprising oxidative addn. into the thiazole C-S bond in a model system.
- 130Ludwig, J. R.; Phan, S.; McAtee, C. C.; Zimmerman, P. M.; Devery, J. J.; Schindler, C. S. Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis Reaction. J. Am. Chem. Soc. 2017, 139, 10832– 10842, DOI: 10.1021/jacs.7b05641130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1egt7jM&md5=4a6fef8b15abcdf907ae50c6cfda4874Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis ReactionLudwig, Jacob R.; Phan, Susan; McAtee, Christopher C.; Zimmerman, Paul M.; Devery, James J., III; Schindler, Corinna S.Journal of the American Chemical Society (2017), 139 (31), 10832-10842CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new approach toward the assembly of mols. traditionally generated by olefin-olefin metathesis or olefination. Herein, we report detailed synthetic, spectroscopic, kinetic, and computational studies to det. the mechanistic features imparted by iron(III), substrate, and temp. to the catalytic cycle. These data are consistent with an iron(III)-mediated asynchronous, concerted [2+2]-cycloaddn. to form an intermediate oxetane as the turnover-limiting step. Fragmentation of the oxetane via Lewis acid-activation results in the formation of five- and six-membered unsatd. carbocycles.
- 131Dewyer, A. L.; Zimmerman, P. M. Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of Piperidine. ACS Catal. 2017, 7, 5466– 5477, DOI: 10.1021/acscatal.7b01390131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1SjtrrL&md5=6411ffbbfdd8b838027c426c5c1ca207Simulated Mechanism for Palladium-Catalyzed, Directed γ-Arylation of PiperidineDewyer, Amanda L.; Zimmerman, Paul M.ACS Catalysis (2017), 7 (8), 5466-5477CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Quantum chem. reaction path finding methods are herein used to investigate the mechanism of Pd-catalyzed distal functionalization of piperidine, as reported by Sanford. These methods allowed navigation of a complex reaction landscape with multiple reactants interacting at all key steps of the proposed catalytic cycle. A multistep cycle is shown to conceptually begin with substrate ligation and Pd(II)-catalyzed C-H activation, which occurs through concerted metalation-deprotonation. In subsequent steps, the kinetic and thermodn. profiles for oxidative addn., reductive elimination, and catalyst regeneration show why excess Cs salts and ArI were required in the expt. Specifically, excess ArI is necessary to thermodynamically overcome the high energy of the C-H activated intermediate and allow oxidative addn. to be favorable, and excess Cs salt is needed to sequester reaction byproducts during oxidative addn. and catalyst regeneration. The overall catalytic profile is consistent with rate-limiting C-H activation, explains the probable functions of all major exptl. conditions, and gives atomistic detail to guide expt. to improve this challenging transformation even further.
- 132Habershon, S. Sampling Reactive Pathways with Random Walks in Chemical Space: Applications to Molecular Dissociation and Catalysis. J. Chem. Phys. 2015, 143, 094106, DOI: 10.1063/1.4929992132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVCms73P&md5=10d9945d033f6fcbdf91a9a4859d4243Sampling reactive pathways with random walks in chemical space: Applications to molecular dissociation and catalysisHabershon, ScottJournal of Chemical Physics (2015), 143 (9), 094106/1-094106/14CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Automatically generating chem. reaction pathways is a significant computational challenge, particularly in the case where a given chem. system can exhibit multiple reactants and products, as well as multiple pathways connecting these. Here, we outline a computational approach to allow automated sampling of chem. reaction pathways, including sampling of different chem. species at the reaction end-points. The key features of this scheme are (i) introduction of a Hamiltonian which describes a reaction "string" connecting reactant and products, (ii) definition of reactant and product species as chem. connectivity graphs, and (iii) development of a scheme for updating the chem. graphs assocd. with the reaction end-points. By performing mol. dynamics sampling of the Hamiltonian describing the complete reaction pathway, we are able to sample multiple different paths in configuration space between given chem. products; by periodically modifying the connectivity graphs describing the chem. identities of the end-points we are also able to sample the allowed chem. space of the system. Overall, this scheme therefore provides a route to automated generation of a "roadmap" describing chem. reactivity. This approach is first applied to model dissocn. pathways in formaldehyde, H2CO, as described by a parameterised potential energy surface (PES). A second application to the HCo(CO)3 catalyzed hydroformylation of ethene (oxo process), using d. functional tight-binding to model the PES, demonstrates that our graph-based approach is capable of sampling the intermediate paths in the commonly accepted catalytic mechanism, as well as several secondary reactions. Further algorithmic improvements are suggested which will pave the way for treating complex multi-step reaction processes in a more efficient manner. (c) 2015 American Institute of Physics.
- 133Habershon, S. Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path Sampling. J. Chem. Theory Comput. 2016, 12, 1786– 1798, DOI: 10.1021/acs.jctc.6b00005133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xjs1Sqtbk%253D&md5=f227bc5d2e1be8e62e71c72bf772bb71Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path SamplingHabershon, ScottJournal of Chemical Theory and Computation (2016), 12 (4), 1786-1798CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)In a recent article [ J. Chem. Phys. 2015, 143, 094106], we introduced a novel graph-based sampling scheme which can be used to generate chem. reaction paths in many-atom systems in an efficient and highly automated manner. The main goal of this work is to demonstrate how this approach, when combined with direct kinetic modeling, can be used to det. the mechanism and phenomenol. rate law of a complex catalytic cycle, namely cobalt-catalyzed hydroformylation of ethene. Our graph-based sampling scheme generates 31 unique chem. products and 32 unique chem. reaction pathways; these sampled structures and reaction paths enable automated construction of a kinetic network model of the catalytic system when combined with d. functional theory (DFT) calcns. of free energies and resultant transition-state theory rate consts. Direct simulations of this kinetic network across a range of initial reactant concns. enables detn. of both the reaction mechanism and the assocd. rate law in an automated fashion, without the need for either presupposing a mechanism or making steady-state approxns. in kinetic anal. Most importantly, we find that the reaction mechanism which emerges from these simulations is exactly that originally proposed by Heck and Breslow; furthermore, the simulated rate law is also consistent with previous exptl. and computational studies, exhibiting a complex dependence on carbon monoxide pressure. While the inherent errors of using DFT simulations to model chem. reactivity limit the quant. accuracy of our calcd. rates, this work confirms that our automated simulation strategy enables direct anal. of catalytic mechanisms from first principles.
- 134Wheeler, S. E.; Seguin, T. J.; Guan, Y.; Doney, A. C. Noncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst Design. Acc. Chem. Res. 2016, 49, 1061– 1069, DOI: 10.1021/acs.accounts.6b00096134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmsFCrsLw%253D&md5=4cffcbf91f93ae4ecaf20537c364fcebNoncovalent Interactions in Organocatalysis and the Prospect of Computational Catalyst DesignWheeler, Steven E.; Seguin, Trevor J.; Guan, Yanfei; Doney, Analise C.Accounts of Chemical Research (2016), 49 (5), 1061-1069CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Noncovalent interactions are ubiquitous in org. systems, and can play decisive roles in the outcome of asym. organocatalytic reactions. Their prevalence, combined with the often subtle line sepg. favorable dispersion interactions from unfavorable steric interactions, often complicates the identification of the particular noncovalent interactions responsible for stereoselectivity. Ultimately, the stereoselectivity of most organocatalytic reactions hinges on the balance of both favorable and unfavorable noncovalent interactions in the stereocontrolling transition state (TS). In this Account, we provide an overview of our attempts to understand the role of noncovalent interactions in organocatalyzed reactions and to develop new computational tools for organocatalyst design. Following a brief discussion of noncovalent interactions involving arom. rings and the assocd. challenges capturing these effects computationally, we summarize two examples of chiral phosphoric acid catalyzed reactions in which noncovalent interactions play pivotal, although somewhat unexpected, roles. In the first, List's catalytic asym. Fischer indole reaction, we show that both π-stacking and CH/π interactions of the substrate with the 3,3'-aryl groups of the catalyst impact the stability of the stereocontrolling TS. However, these noncovalent interactions oppose each other, with π-stacking interactions stabilizing the TS leading to one enantiomer and CH/π interactions preferentially stabilizing the competing TS. Ultimately, the CH/π interactions dominate and, when combined with hydrogen bonding interactions, lead to preferential formation of the obsd. product. In the second example, a series of phosphoric acid catalyzed asym. ring openings of meso-epoxides, we show that noncovalent interactions of the substrates with the 3,3'-aryl groups of the catalyst play only an indirect role in stereoselectivity. Instead, the stereoselectivity of these reactions are driven by the electrostatic stabilization of a fleeting partial pos. charge in the SN2-like transition state by the chiral electrostatic environment of the phosphoric acid catalyst. Next, we describe our studies of bipyridine N-oxide and N,N'-dioxide catalyzed alkylation reactions. Based on several examples, we demonstrate that there are many potential arrangements of ligands around a hexacoordinate silicon in the stereocontrolling TS, and one must consider all of these in order to identify the lowest-lying TS structures. We also present a model in which electrostatic interactions between a formyl CH group and a chlorine in these TSs underlie the enantioselectivity of these reactions. Finally, we discuss our efforts to develop computational tools for the screening of potential organocatalyst designs, starting in the context of bipyridine N,N'-dioxide catalyzed alkylation reactions. Our new computational tool kit (AARON) has been used to design highly effective catalysts for the asym. propargylation of benzaldehyde, and is currently being used to screen catalysts for other reactions. We conclude with our views on the potential roles of computational chem. in the future of organocatalyst design.
- 135Doney, A. C.; Rooks, B. J.; Lu, T.; Wheeler, S. E. Design of Organocatalysts for Asymmetric Propargylations through Computational Screening. ACS Catal. 2016, 6, 7948– 7955, DOI: 10.1021/acscatal.6b02366135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yks7jO&md5=207d00d90bba03b6dfeed14f3762364aDesign of Organocatalysts for Asymmetric Propargylations through Computational ScreeningDoney, Analise C.; Rooks, Benjamin J.; Lu, Tongxiang; Wheeler, Steven E.ACS Catalysis (2016), 6 (11), 7948-7955CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)The development of asym. catalysts is typically driven by the exptl. screening of potential catalyst designs. Herein, the authors demonstrate the design of asym. propargylation catalysts through computational screening. This was done using computational toolkit AARON (automated alkylation reaction optimizer for N-oxides), which automates the prediction of enantioselectivities for bidentate Lewis base catalyzed alkylation reactions. A systematic screening of 59 potential catalysts built on 6 bipyridine N,N'-dioxide-derived scaffolds results in predicted ee values for the propargylation of benzaldehyde ranging from 45% (S) to 99% (R), with 12 ee values exceeding 95%. These data provide a broad set of exptl. testable predictions. Also, the assocd. data revealed key details regarding the role of stabilizing electrostatic interactions in asym. propargylations, which were harnessed in the design of a propargylation catalyst for which the predicted ee exceeds 99%.
- 136Guan, Y.; Wheeler, S. E. Automated Quantum Mechanical Predictions of Enantioselectivity in a Rhodium-Catalyzed Asymmetric Hydrogenation. Angew. Chem. 2017, 129, 9229– 9233, DOI: 10.1002/ange.201704663There is no corresponding record for this reference.
- 137Guan, Y.; Ingman, V. M.; Rooks, B. J.; Wheeler, S. E. AARON: An Automated Reaction Optimizer for New Catalysts. J. Chem. Theory Comput. 2018, 14, 5249, DOI: 10.1021/acs.jctc.8b00578137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVOlsbbO&md5=f8e15c28a5e202415fbb232e93310a79AARON: An Automated Reaction Optimizer for New CatalystsGuan, Yanfei; Ingman, Victoria M.; Rooks, Benjamin J.; Wheeler, Steven E.Journal of Chemical Theory and Computation (2018), 14 (10), 5249-5261CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)We describe an open-source computational toolkit (AARON: An Automated Reaction Optimizer for New catalysts) that automates the quantum mech. geometry optimization and characterization of the transition state and intermediate structures required to predict the activities and selectivities of asym. catalytic reactions. Modern computational quantum chem. has emerged as a powerful tool for explaining the selectivity and activity of asym. catalysts. However, reliably predicting the stereochem. outcome of realistic reactions often requires the geometry optimization of hundreds of transition state and intermediate structures, which is a tedious process. AARON automates these optimizations through an interface with a popular electronic structure package, accelerating quantum chem. workflows to enable the computational screening of potential catalysts. AARON is built using a collection of object-oriented Perl modules (AaronTools) that provide functionality to build and modify mol. and supramol. structures. The main functionalities of AaronTools are also available as stand-alone command-line scripts. The core features of AaronTools and AARON are explained, and representative applications of AARON to both organocatalyzed and transition-metal-catalyzed reactions are presented.
- 138Geerlings, P.; De Proft, F.; Langenaeker, W. Conceptual Density Functional Theory. Chem. Rev. 2003, 103, 1793– 1874, DOI: 10.1021/cr990029p138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXivFGgu7g%253D&md5=085c8ae5893c0b05158629e182ecb0a4Conceptual Density Functional TheoryGeerlings, P.; De Proft, F.; Langenaeker, W.Chemical Reviews (Washington, DC, United States) (2003), 103 (5), 1793-1873CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on conceptual d. functional theory including the following topics: fundamental and computational aspects of DFT, DFT-based concepts and principles and applications of DFT.
- 139Geerlings, P.; Proft, F. D. Conceptual DFT: The Chemical Relevance of Higher Response Functions. Phys. Chem. Chem. Phys. 2008, 10, 3028– 3042, DOI: 10.1039/b717671f139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtVKmt7o%253D&md5=d0abd6b5a14679da7da2cef53918a636Conceptual DFT: the chemical relevance of higher response functionsGeerlings, P.; De Proft, F.Physical Chemistry Chemical Physics (2008), 10 (21), 3028-3042CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)A review. In recent years conceptual d. functional theory offered a perspective for the interpretation/prediction of exptl./theor. reactivity data on the basis of a series of response functions to perturbations in the no. of electrons and/or external potential. This approach has enabled the sharp definition and computation, from first principles, of a series of well-known but sometimes vaguely defined chem. concepts such as electronegativity and hardness. In this contribution, a short overview of the shortcomings of the simplest, first-order response functions is illustrated leading to a description of chem. bonding in a covalent interaction in terms of interacting atoms or groups, governed by electrostatics with the tendency to polarize bonds on the basis of electronegativity differences. The second order approach, well known until now, introduces the hardness/softness and Fukui function concepts related to polarizability and frontier MO theory, resp. The introduction of polarizability/softness is also considered in a historical perspective in which polarizability was, with some exceptions, mainly put forward in non covalent interactions. A particular series of response functions, arising when the changes in the external potential are solely provoked by changes in nuclear configurations (the "R-analogs") are also systematically considered. The main part of the contribution is devoted to third-order response functions which, at first sight, may be expected not to yield chem. significant information, as turns out to be for the hyperhardness. A counterexample is the dual descriptor and its R analog, the initial hardness response, which turns out to yield a firm basis to regain the Woodward-Hoffmann rules for pericyclic reactions based on a d.-only basis, i.e. without involving the phase, sign, symmetry of the wavefunction. Even the second-order nonlinear response functions are shown possibly to bear interesting information, e.g. on the local and global polarizability. Its derivs. may govern the influence of charge on the polarizability, the R-analogs being the nuclear Fukui function and the quadratic and cubic force consts. Although some of the higher order derivs. may be difficult to evaluate a comparison with the energy expansion used in spectroscopy in terms of nuclear displacements, nuclear magnetic moments, elec. and magnetic fields leads to the conjecture that, certainly cross terms may contain new, intricate information for understanding chem. reactivity.
- 140Proft, F. D.; Ayers, P. W.; Geerlings, P. The Chemical Bond; Wiley-Blackwell, 2014; pp 233– 270.There is no corresponding record for this reference.
- 141Bergeler, M.; Simm, G. N.; Proppe, J.; Reiher, M. Heuristics-Guided Exploration of Reaction Mechanisms. J. Chem. Theory Comput. 2015, 11, 5712– 5722, DOI: 10.1021/acs.jctc.5b00866141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslCjtbjO&md5=c283427244c99d448f5c895d6f434b06Heuristics-Guided Exploration of Reaction MechanismsBergeler, Maike; Simm, Gregor N.; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2015), 11 (12), 5712-5722CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For the investigation of chem. reaction networks, the efficient and accurate detn. of all relevant intermediates and elementary reactions is mandatory. The complexity of such a network may grow rapidly, in particular if reactive species are involved that might cause a myriad of side reactions. Without automation, a complete investigation of complex reaction mechanisms is tedious and possibly unfeasible. Therefore, only the expected dominant reaction paths of a chem. reaction network (e.g., a catalytic cycle or an enzymic cascade) are usually explored in practice. Here, we present a computational protocol that constructs such networks in a parallelized and automated manner. Mol. structures of reactive complexes are generated based on heuristic rules derived from conceptual electronic-structure theory and subsequently optimized by quantum-chem. methods to produce stable intermediates of an emerging reaction network. Pairs of intermediates in this network that might be related by an elementary reaction according to some structural similarity measure are then automatically detected and subjected to an automated search for the connecting transition state. The results are visualized as an automatically generated network graph, from which a comprehensive picture of the mechanism of a complex chem. process can be obtained that greatly facilitates the anal. of the whole network. We apply our protocol to the Schrock dinitrogen-fixation catalyst to study alternative pathways of catalytic ammonia prodn.
- 142Gánti, T. Organization of Chemical Reactions into Dividing and Metabolizing Units: The Chemotons. BioSystems 1975, 7, 15– 21, DOI: 10.1016/0303-2647(75)90038-6There is no corresponding record for this reference.
- 143Yandulov, D. V.; Schrock, R. R. Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine Complex. J. Am. Chem. Soc. 2002, 124, 6252– 6253, DOI: 10.1021/ja020186x143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XjsVyhsb8%253D&md5=5a7abc5e8c8135193ceb83918f21ea43Reduction of Dinitrogen to Ammonia at a Well-Protected Reaction Site in a Molybdenum Triamidoamine ComplexYandulov, Dmitry V.; Schrock, Richard R.Journal of the American Chemical Society (2002), 124 (22), 6252-6253CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We have synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (HexaIsoPropylTerphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 led to formation of orange [HIPTN3N]MoCl. Redn. of [HIPTN3N]MoCl with magnesium in THF under dinitrogen led to formation of salts that contain the {[HIPTN3N]Mo(N2)}- ion. The {[HIPTN3N]Mo(N2)}- ion can be oxidized by zinc chloride to give [HIPTN3N]Mo(N2) or protonated to give [HIPTN3N]Mo-N:N-H. Other relevant compds. that have been prepd. include {[HIPTN3N]Mo-N:NH2}+, [HIPTN3N]Mo≡N, {[HIPTN3N]Mo:NH}+, and {[HIPTN3N]Mo(NH3)}+. (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-.). Redn. of [HIPTN3N]Mo(N2) with CoCp2 in the presence of {2,6-lutidinium}BAr'4 in benzene leads to formation of ammonia and {[HIPTN3N]Mo(NH3)}+. Preliminary X-ray studies suggest that the HIPT substituent creates a deep, three-fold sym. cavity that protects a variety of dinitrogen redn. products against bimol. decompn. reactions, while at the same time the metal is left relatively open toward reactions near the equatorial amido ligands.
- 144Yandulov, D. V.; Schrock, R. R.; Rheingold, A. L.; Ceccarelli, C.; Davis, W. M. Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl Substituents. Inorg. Chem. 2003, 42, 796– 813, DOI: 10.1021/ic020505l144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjt1yqtg%253D%253D&md5=224f2e5ebc46cf53c66ce1e68f6de311Synthesis and Reactions of Molybdenum Triamidoamine Complexes Containing Hexaisopropylterphenyl SubstituentsYandulov, Dmitry V.; Schrock, Richard R.; Rheingold, Arnold L.; Ceccarelli, Christopher; Davis, William M.Inorganic Chemistry (2003), 42 (3), 796-813CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)The authors synthesized a triamidoamine ligand ([(RNCH2CH2)3N]3-) in which R is 3,5-(2,4,6-i-Pr3C6H2)2C6H3 (hexaisopropylterphenyl or HIPT). The reaction between MoCl4(THF)2 and H3[HIPTN3N] in THF followed by 3.1 equiv of LiN(SiMe3)2 gave orange [HIPTN3N]MoCl. Redn. of MoCl (Mo = [HIPTN3N]Mo) with Mg in THF under dinitrogen gave salts that contain the {Mo(N2)}- ion. The {Mo(N2)}- ion can be oxidized by ZnCl2 to give Mo(N2) or protonated to give MoN:NH. The latter decomps. to yield MoH. Other relevant compds. that were prepd. include {Mo:N-NH2}+ (by protonation of MoN:NH), Mo≡N, {Mo=NH}+ (by protonation of Mo≡N), and {Mo(NH3)}+ (by treating MoCl with NH3) (The anion is usually {B(3,5-(CF3)2C6H3)4}- = {BAr'4}-). X-ray studies were carried out on {Mg(DME)3}0.5[Mo(N2)], MoN:NMgBr(THF)3, Mo(N2), Mo≡N, and {Mo(NH3)}{BAr'4}. Probably the HIPT substituent on the triamidoamine ligand creates a cavity that stabilizes a variety of complexes that might be encountered in a hypothetical Chatt-like dinitrogen redn. scheme, perhaps largely by protecting against bimol. decompn. reactions.
- 145Eschenmoser, A.; Loewenthal, E. Chemistry of Potentially Prebiological Natural Products. Chem. Soc. Rev. 1992, 21, 1– 16, DOI: 10.1039/cs9922100001145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38Xht1egtL4%253D&md5=26e2c8a468693ecdbff4a3b01d3766beChemistry of potentially prebiological natural productsEschenmoser, Albert; Loewenthal, EliChemical Society Reviews (1992), 21 (1), 1-16CODEN: CSRVBR; ISSN:0306-0012.A review with 59 refs. on the title subject with regard to sugar phosphates, purines, pyrimidines and oligonucleotides.
- 146Delidovich, I. V.; Simonov, A. N.; Taran, O. P.; Parmon, V. N. Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis. ChemSusChem 2014, 7, 1833– 1846, DOI: 10.1002/cssc.201400040146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslGjtLw%253D&md5=3f51d7aa82ef147a6e790097a698e7c5Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective SynthesisDelidovich, Irina V.; Simonov, Alexandr N.; Taran, Oxana P.; Parmon, Valentin N.ChemSusChem (2014), 7 (7), 1833-1846CODEN: CHEMIZ; ISSN:1864-5631. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The formose reaction (FR) was long the focus of intensive studies as a simple method for synthesis of complex biol. important monosaccharides and other sugar-like mols. from the simplest org. substrate-formaldehyde. The fundamental importance of the FR is predominantly connected with the ascertainment of plausible scenarios of chem. evolution which could occurred on the prebiotic Earth to produce the very first mols. of carbohydrates, amino- and nucleic acids, as well as other vitally important substances. The practical importance of studies on the FR is the elaboration of catalytic methods for the synthesis of rare and nonnatural monosaccharides and polyols. This Minireview considers the FR from the point of view of chemists working in the field of catalysis with emphasis on the mechanisms of numerous parallel and consequent catalytic transformations that take place during the FR. Based on its kinetics, the FR may be considered as a nonradical chain process with degenerate branching. The Minireview also considers different approaches to the control of selectivity of carbohydrate synthesis from formaldehyde and lower monosaccharides.
- 147Simm, G. N.; Reiher, M. Context-Driven Exploration of Complex Chemical Reaction Networks. J. Chem. Theory Comput. 2017, 13, 6108– 6119, DOI: 10.1021/acs.jctc.7b00945147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsleiurfJ&md5=1a898dab5d04f2c4889afb549a4dbb5aContext-Driven Exploration of Complex Chemical Reaction NetworksSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (12), 6108-6119CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The construction of a reaction network contg. all relevant intermediates and elementary reactions is necessary for the accurate description of chem. processes. In the case of a complex chem. reaction (involving, for instance, many reactants or highly reactive species), the size of such a network may grow rapidly. Here, we present a computational protocol that constructs such reaction networks in a fully automated fashion steered in an intuitive, graph-based fashion through a single graphical user interface. Starting from a set of initial reagents new intermediates are explored through intra- and intermol. reactions of already explored intermediates or new reactants presented to the network. This is done by assembling reactive complexes based on heuristic rules derived from conceptual electronic-structure theory and exploring the corresponding approx. reaction path. A subsequent path refinement leads to a min.-energy path which connects the new intermediate to the existing ones to form a connected reaction network. Tree traversal algorithms are then employed to detect reaction channels and catalytic cycles. We apply our protocol to the formose reaction to study different pathways of sugar formation and to rationalize its autocatalytic nature.
- 148Proppe, J.; Reiher, M. Mechanism Deduction from Noisy Chemical Reaction Networks. J. Chem. Theory Comput. 2018, submitted, [arXiv: 1803.09346].There is no corresponding record for this reference.
- 149Husch, T.; Vaucher, A. C.; Reiher, M. Semiempirical Molecular Orbital Models based on the Neglect of Diatomic Differential Overlap Approximation. Int. J. Quantum Chem. 2018, e25799 DOI: 10.1002/qua.25799There is no corresponding record for this reference.
- 150Husch, T.; Reiher, M. Comprehensive analysis of the neglect of diatomic differential overlap approximation. J. Chem. Theory Comput. 2018, 14, 5169– 5179, DOI: 10.1021/acs.jctc.8b00601150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1KhtbzI&md5=1410f3e6922bfcc2d97eb12e6ebbb005Comprehensive Analysis of the Neglect of Diatomic Differential Overlap ApproximationHusch, Tamara; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5169-5179CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Many modern semiempirical MO models are built on the NDDO approxn. An in-depth understanding of this approxn. is therefore indispensable to rationalize the success of these semiempirical MO models and to develop further improvements on them. The NDDO approxn. provides a recipe to approx. electron-electron repulsion integrals (ERIs) in a sym. orthogonalized basis based on a far smaller no. of ERIs in a locally orthogonalized basis. We first analyze the NDDO approxn. by comparing ERIs in both bases for a selection of mols. and for a selection of basis sets. We find that the errors in Hartree-Fock and second-order Moller-Plesset perturbation theory energies grow roughly linearly with the no. of basis functions. We then examine different approaches to correct for the errors caused by the NDDO approxn. and propose a strategy to directly correct for them in the two-electron matrixes that enter the Fock operator.
- 151Simm, G. N.; Proppe, J.; Reiher, M. Error Assessment of Computational Models in Chemistry. Chimia 2017, 71, 202– 208, DOI: 10.2533/chimia.2017.202151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1ajt7rK&md5=88488125dbc1ae5214a8b22d52d9570bError assessment of computational models in chemistrySimm, Gregor N.; Proppe, Jonny; Reiher, MarkusChimia (2017), 71 (4), 202-208CODEN: CHIMAD ISSN:. (Swiss Chemical Society)Computational models in chem. rely on a no. of approxns. The effect of such approxns. on observables derived from them is often unpredictable. Therefore, it is challenging to quantify the uncertainty of a computational result, which, however, is necessary to assess the suitability of a computational model. Common performance statistics such as the mean abs. error are prone to failure as they do not distinguish the explainable (systematic) part of the errors from their unexplainable (random) part. In this paper, we discuss problems and solns. for performance assessment of computational models based on several examples from the quantum chem. literature. For this purpose, we elucidate the different sources of uncertainty, the elimination of systematic errors, and the combination of individual uncertainty components to the uncertainty of a prediction.
- 152Proppe, J.; Reiher, M. Reliable Estimation of Prediction Uncertainty for Physicochemical Property Models. J. Chem. Theory Comput. 2017, 13, 3297– 3317, DOI: 10.1021/acs.jctc.7b00235152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXpt1ykt7w%253D&md5=41bb917d7e3707ab9c6308a00dd056c9Reliable Estimation of Prediction Uncertainty for Physicochemical Property ModelsProppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (7), 3297-3317CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)One of the major challenges in computational science is to det. the uncertainty of a virtual measurement, that is the prediction of an observable based on calcns. As highly accurate first-principles calcns. are in general unfeasible for most phys. systems, one usually resorts to parameteric property models of observables, which require calibration by incorporating ref. data. The resulting predictions and their uncertainties are sensitive to systematic errors such as inconsistent ref. data, parametric model assumptions, or inadequate computational methods. Here, we discuss the calibration of property models in the light of bootstrapping, a sampling method that can be employed for identifying systematic errors and for reliable estn. of the prediction uncertainty. We apply bootstrapping to assess a linear property model linking the 57Fe Mossbauer isomer shift to the contact electron d. at the iron nucleus for a diverse set of 44 mol. iron compds. The contact electron d. is calcd. with 12 d. functionals across Jacob's ladder (PWLDA, BP86, BLYP, PW91, PBE, M06-L, TPSS, B3LYP, B3PW91, PBE0, M06, TPSSh). We provide systematic-error diagnostics and reliable, locally resolved uncertainties for isomer-shift predictions. Pure and hybrid d. functionals yield av. prediction uncertainties of 0.06-0.08 mm s-1 and 0.04-0.05 mm s-1, resp., the latter being close to the av. exptl. uncertainty of 0.02 mm s-1. Furthermore, we show that both model parameters and prediction uncertainty depend significantly on the compn. and no. of ref. data points. Accordingly, we suggest that rankings of d. functionals based on performance measures (e.g., the squared coeff. of correlation, r2, or the root-mean-square error, RMSE) should not be inferred from a single data set. This study presents the first statistically rigorous calibration anal. for theor. Mossbauer spectroscopy, which is of general applicability for physicochem. property models and not restricted to isomer-shift predictions. We provide the statistically meaningful ref. data set MIS39 and a new calibration of the isomer shift based on the PBE0 functional.
- 153Weymuth, T.; Proppe, J.; Reiher, M. Statistical Analysis of Semiclassical Dispersion Corrections. J. Chem. Theory Comput. 2018, 14, 2480– 2494, DOI: 10.1021/acs.jctc.8b00078153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmvVaqsL4%253D&md5=723d9ba5398927668bdedd0141a9b508Statistical Analysis of Semiclassical Dispersion CorrectionsWeymuth, Thomas; Proppe, Jonny; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (5), 2480-2494CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Semiclassical dispersion corrections developed by Grimme and co-workers have become indispensable in applications of Kohn-Sham d. functional theory. A deeper understanding of the underlying parametrization might be crucial for well-founded further improvements of this successful approach. To this end, we present an in-depth assessment of the fit parameters present in semiclassical (D3-type) dispersion corrections by means of a statistically rigorous anal. We find that the choice of the cost function generally has a small effect on the empirical parameters of D3-type dispersion corrections with respect to the ref. set under consideration. Only in a few cases, the choice of cost function has a surprisingly large effect on the total dispersion energies. In particular, the weighting scheme in the cost function can significantly affect the reliability of predictions. In order to obtain unbiased (data-independent) uncertainty ests. for both the empirical fit parameters and the corresponding predictions, we carried out a nonparametric bootstrap anal. This anal. reveals that the std. deviation of the mean of the empirical D3 parameters is small. Moreover, the mean prediction uncertainty obtained by bootstrapping is not much larger than previously reported error measures. On the basis of a jackknife anal., we find that the original ref. set is slightly skewed, but our results also suggest that this feature hardly affects the prediction of dispersion energies. Furthermore, we find that the introduction of small uncertainties to the ref. data does not change the conclusions drawn in this work. However, a rigorous anal. of error accumulation arising from different parametrizations reveals that error cancellation does not necessarily occur, leading to a monotonically increasing deviation in the dispersion energy with increasing mol. size. We discuss this issue in detail at the prominent example of the C60 "buckycatcher". We find deviations between individual parametrizations of several tens of kilocalories per mol in some cases. Hence, in combination with any calcn. of dispersion energies, we recommend to always det. the assocd. uncertainties for which we will provide a software tool.
- 154Proppe, J.; Husch, T.; Simm, G. N.; Reiher, M. Uncertainty quantification for quantum chemical models of complex reaction networks. Faraday Discuss. 2016, 195, 497– 520, DOI: 10.1039/C6FD00144K154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFantbbF&md5=72ef620f8bd4517eb0c2c46fa32a05afUncertainty quantification for quantum chemical models of complex reaction networksProppe, Jonny; Husch, Tamara; Simm, Gregor N.; Reiher, MarkusFaraday Discussions (2016), 195 (Reaction Rate Theory), 497-520CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)A review. For the quant. understanding of complex chem. reaction mechanisms, it is, in general, necessary to accurately det. the corresponding free energy surface and to solve the resulting continuous-time reaction rate equations for a continuous state space. For a general (complex) reaction network, it is computationally hard to fulfill these two requirements. However, it is possible to approx. address these challenges in a phys. consistent way. On the one hand, it may be sufficient to consider approx. free energies if a reliable uncertainty measure can be provided. On the other hand, a highly resolved time evolution may not be necessary to still det. quant. fluxes in a reaction network if one is interested in specific time scales. In this paper, we present discrete-time kinetic simulations in discrete state space taking free energy uncertainties into account. The method builds upon thermo-chem. data obtained from electronic structure calcns. in a condensed-phase model. Our kinetic approach supports the anal. of general reaction networks spanning multiple time scales, which is here demonstrated for the example of the formose reaction. An important application of our approach is the detection of regions in a reaction network which require further investigation, given the uncertainties introduced by both approx. electronic structure methods and kinetic models. Such cases can then be studied in greater detail with more sophisticated first-principles calcns. and kinetic simulations.
- 155Simm, G.; Reiher, M. Error-Controlled Exploration of Chemical Reaction Networks with Gaussian Processes. J. Chem. Theory Comput. 2018, 14, 5238– 5248, DOI: 10.1021/acs.jctc.8b00504155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1Gmt7vK&md5=116ed9b1481210ec5564eb6e1d0157f8Error-Controlled Exploration of Chemical Reaction Networks with Gaussian ProcessesSimm, Gregor N.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (10), 5238-5248CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)For a theor. understanding of the reactivity of complex chem. systems, relative energies of stationary points on potential energy hypersurfaces need to be calcd. to high accuracy. Due to the large no. of intermediates present in all but the simplest chem. processes, approx. quantum chem. methods are required that allow for fast evaluations of the relative energies but at the expense of accuracy. Despite the plethora of benchmark studies, the accuracy of a quantum chem. method is often difficult to assess. Moreover, a significant improvement of a method's accuracy (e.g., through reparameterization or systematic model extension) is rarely possible. Here, we present a new approach that allows for the systematic, problem-oriented, and rolling improvement of quantum chem. results through the application of Gaussian processes. Due to its Bayesian nature, reliable error ests. are provided for each prediction. A ref. method of high accuracy can be employed if the uncertainty assocd. with a particular calcn. is above a given threshold. The new data point is then added to a growing data set in order to continuously improve the model and, as a result, all subsequent predictions. Previous predictions are validated by the updated model to ensure that uncertainties remain within the given confidence bound, which we call backtracking. We demonstrate our approach with the example of a complex chem. reaction network.
- 156Lagorce, D.; Pencheva, T.; Villoutreix, B. O.; Miteva, M. A. DG-AMMOS: A New Tool to Generate 3D Conformation of Small Molecules Using Distance Geometry and Automated Molecular Mechanics Optimization for in Silico Screening. BMC Chem. Biol. 2009, 9, 6, DOI: 10.1186/1472-6769-9-6156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjnsVKrtA%253D%253D&md5=6722e659d6b334955fbc5239df28e37fDG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screeningLagorce David; Villoutreix Bruno O; Miteva Maria A; Pencheva TaniaBMC chemical biology (2009), 9 (), 6 ISSN:.BACKGROUND: Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. RESULTS: Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. CONCLUSION: DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.
- 157Riniker, S.; Landrum, G. A. Better Informed Distance Geometry: Using What We Know To Improve Conformation Generation. J. Chem. Inf. Model. 2015, 55, 2562– 2574, DOI: 10.1021/acs.jcim.5b00654157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVeqsrjP&md5=8ee6d7d1999924fc2b42f76577f8ec51Better Informed Distance Geometry: Using What We Know To Improve Conformation GenerationRiniker, Sereina; Landrum, Gregory A.Journal of Chemical Information and Modeling (2015), 55 (12), 2562-2574CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Small org. mols. are often flexible, i.e., they can adopt a variety of low-energy conformations in soln. that exist in equil. with each other. Two main search strategies are used to generate representative conformational ensembles for mols.: systematic and stochastic. In the first approach, each rotatable bond is sampled systematically in discrete intervals, limiting its use to mols. with a small no. of rotatable bonds. Stochastic methods, however, sample the conformational space of a mol. randomly and can thus be applied to more flexible mols. Different methods employ different degrees of exptl. data for conformer generation. So-called knowledge-based methods use predefined libraries of torsional angles and ring conformations. In the distance geometry approach, however, a smaller amt. of empirical information was used, i.e., ideal bond lengths, ideal bond angles, and a few ideal torsional angles. Distance geometry is a computationally fast method to generate conformers, but it has the downside that purely distance-based constraints tend to lead to distorted arom. rings and sp2 centers. To correct this, the resulting conformations are often minimized with a force field, adding computational complexity and run time. Here the authors present an alternative strategy that combines the distance geometry approach with exptl. torsion-angle preferences obtained from small-mol. crystallog. data. The torsional angles are described by a previously developed set of hierarchically structured SMARTS patterns. The new approach is implemented in the open-source cheminformatics library RDKit, and its performance is assessed by comparing the diversity of the generated ensemble and the ability to reproduce crystal conformations taken from the crystal structures of small mols. and protein-ligand complexes.
- 158Vainio, M. J.; Johnson, M. S. Generating Conformer Ensembles Using a Multiobjective Genetic Algorithm. J. Chem. Inf. Model. 2007, 47, 2462– 2474, DOI: 10.1021/ci6005646158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVOnsL7L&md5=e621e6eedf3d93ff6236bc4887f25e35Generating Conformer Ensembles Using a Multiobjective Genetic AlgorithmVainio, Mikko J.; Johnson, Mark S.Journal of Chemical Information and Modeling (2007), 47 (6), 2462-2474CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The task of generating a nonredundant set of low-energy conformations for small mols. is of fundamental importance for many mol. modeling and drug-design methodologies. Several approaches to conformer generation have been published. Exhaustive searches suffer from the exponential growth of the search space with increasing degrees of conformational freedom (no. of rotatable bonds). Stochastic algorithms do not suffer as much from the exponential increase of search space and provide a good coverage of the energy min. Here, the use of a multiobjective genetic algorithm in the generation of conformer ensembles is investigated. Distance geometry is used to generate an initial conformer, which is then subject to geometric modifications encoded by the individuals of the genetic algorithm. The geometric modifications apply to torsion angles about rotatable bonds, stereochem. of double bonds and tetrahedral chiral centers, and ring conformations. The geometric diversity of the evolving conformer ensemble is preserved by a fitness-sharing mechanism based on the root-mean-square distance of the at. coordinates. Mol. symmetry is taken into account in the distance calcn. The geometric modifications introduce strain into the structures. The strain is relaxed using an MMFF94-like force field in a postprocessing step that also removes conformational duplicates and structures whose strain energy remains above a predefined window from the min. energy value found in the set. The implementation, called Balloon, is available free of charge on the Internet (http://www.abo.fi/∼mivainio/balloon/).
- 159Leite, T. B.; Gomes, D.; Miteva, M. A.; Chomilier, J.; Villoutreix, B. O.; Tufféry, P. Frog: A FRee Online druG 3D Conformation Generator. Nucleic Acids Res. 2007, 35, W568– W572, DOI: 10.1093/nar/gkm289There is no corresponding record for this reference.
- 160Miteva, M. A.; Guyon, F.; Tufféry, P. Frog2: Efficient 3D Conformation Ensemble Generator for Small Compounds. Nucleic Acids Res. 2010, 38, W622– W627, DOI: 10.1093/nar/gkq325160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXotVSqsr8%253D&md5=ec1c9860de9eb1e81e9e8d81f24f550bFrog2: Efficient 3D conformation ensemble generator for small compoundsMiteva, Maria A.; Guyon, Frederic; Tuffery, PierreNucleic Acids Research (2010), 38 (Web Server), W622-W627CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)Frog is a web tool dedicated to small compd. 3D generation. Here we present the new version, Frog2, which allows the generation of conformation ensembles of small mols. starting from either 1D, 2D or 3D description of the compds. From a compd. description in one of the SMILES, SDF or mol2 formats, the server will return an ensemble of diverse conformers generated using a two stage Monte Carlo approach in the dihedral space. When starting from 1D or 2D description of compds., Frog2 is capable to detect the sites of ambiguous stereoisomery, and thus to sample different stereoisomers. Frog2 also embeds new energy minimization and ring generation facilities that solve the problem of some missing cycle structures in the Frog1 ring library. Finally, the optimized generator of conformation ensembles in Frog2 results in a gain of computational time permitting Frog2 to be up to 20 times faster that Frog1, while producing satisfactory conformations in terms of structural quality and conformational diversity. The high speed and the good quality of generated conformational ensembles makes it possible the treatment of larger compd. collections using Frog2. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/Frog2.
- 161Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model. 2010, 50, 572– 584, DOI: 10.1021/ci100031x161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjtlaisrY%253D&md5=fb87ecc9c51eddef63b41fffcd9babeeConformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural DatabaseHawkins, Paul C. D.; Skillman, A. Geoffrey; Warren, Gregory L.; Ellingson, Benjamin A.; Stahl, Matthew T.Journal of Chemical Information and Modeling (2010), 50 (4), 572-584CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Here, we present the algorithm and validation for OMEGA, a systematic, knowledge-based conformer generator. The algorithm consists of three phases: assembly of an initial 3D structure from a library of fragments; exhaustive enumeration of all rotatable torsions using values drawn from a knowledge-based list of angles, thereby generating a large set of conformations; and sampling of this set by geometric and energy criteria. Validation of conformer generators like OMEGA has often been undertaken by comparing computed conformer sets to exptl. mol. conformations from crystallog., usually from the Protein Databank (PDB). Such an approach is fraught with difficulty due to the systematic problems with small mol. structures in the PDB. Methods are presented to identify a diverse set of small mol. structures from cocomplexes in the PDB that has maximal reliability. A challenging set of 197 high quality, carefully selected ligand structures from well-solved models was obtained using these methods. This set will provide a sound basis for comparison and validation of conformer generators in the future. Validation results from this set are compared to the results using structures of a set of druglike mols. extd. from the Cambridge Structural Database (CSD). OMEGA is found to perform very well in reproducing the crystallog. conformations from both these data sets using two complementary metrics of success.
- 162Schärfer, C.; Schulz-Gasch, T.; Hert, J.; Heinzerling, L.; Schulz, B.; Inhester, T.; Stahl, M.; Rarey, M. CONFECT: Conformations from an Expert Collection of Torsion Patterns. ChemMedChem 2013, 8, 1690– 1700, DOI: 10.1002/cmdc.201300242162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sfotVymtA%253D%253D&md5=9aed22ca5ec1872aea505dadb9d99baeCONFECT: conformations from an expert collection of torsion patternsScharfer Christin; Schulz-Gasch Tanja; Hert Jerome; Heinzerling Lennart; Schulz Benjamin; Inhester Therese; Stahl Martin; Rarey MatthiasChemMedChem (2013), 8 (10), 1690-700 ISSN:.The generation of sets of low-energy conformations for a given molecule is a central task in drug design. Herein we present a new conformation generator called CONFECT that builds on our previously published library of torsion patterns. Conformations are generated as well as ranked by means of normalized frequency distributions derived from the Cambridge Structural Database (CSD). Following an incremental construction approach, conformations are selected from a systematic enumeration within energetic boundaries. The new tool is benchmarked in several different ways, indicating that it allows the efficient generation of high-quality conformation ensembles. These ensembles are smaller than those produced by state-of-the-art tools, yet they effectively cover conformational space.
- 163Guba, W.; Meyder, A.; Rarey, M.; Hert, J. Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules. J. Chem. Inf. Model. 2016, 56, 1– 5, DOI: 10.1021/acs.jcim.5b00522163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XovFKjsA%253D%253D&md5=0e26d363bad3069851a04bf977027f53Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small MoleculesGuba, Wolfgang; Meyder, Agnes; Rarey, Matthias; Hert, JeromeJournal of Chemical Information and Modeling (2016), 56 (1), 1-5CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)The Torsion Library contains hundreds of rules for small mol. conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by mol. design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have systematically revised all torsion rules to better identify highly strained conformations and minimize the no. of false alerts for CSD small mol. X-ray structures. For this new release, we added or substantially modified 78 torsion patterns and reviewed all angles and tolerance intervals. The overall no. of red alerts for a filtered CSD data set with 130 000 structures was reduced by a factor of 4 compared to the predecessor. This is of clear advantage in 3D virtual screening where hits should only be removed by a conformational filter if they are in energetically inaccessible conformations.
- 164Batter, J.; Brooks, F. GROPE-I: A Computer Display to the Sense of Feel. Proceedings of the International Federation of Information Processing 1971, 759– 763There is no corresponding record for this reference.
- 165Noll, A. M. Man-Machine Tactile Communication. J. Soc. Inform. Dis. 1972, 6–11, 30There is no corresponding record for this reference.
- 166Atkinson, W. D.; Bond, K. E.; Tribble, G. L.; Wilson, K. R. Computing with Feeling. Comp. and Graph. 1977, 2, 97– 103, DOI: 10.1016/0097-8493(77)90009-7There is no corresponding record for this reference.
- 167Lancaster, S. J. Immersed in virtual molecules. Nature Rev. Chem. 2018, 2, 253– 254, DOI: 10.1038/s41570-018-0043-5167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVKnsb3M&md5=886aaa061e23d04e29d0b2bdc99df026Immersed in virtual moleculesLancaster, Simon J.Nature Reviews Chemistry (2018), 2 (10), 253-254CODEN: NRCAF7; ISSN:2397-3358. (Nature Research)A full grasp of chem. requires students to be able to connect microscopic reality with symbolic representations. Immersive virtual reality provides a soln. for those who need a tangible link between these representations.
- 168Aspuru-Guzik, A.; Lindh, R.; Reiher, M. The Matter (R)evolution. ACS Cent. Sci. 2018, 4, 144– 152, DOI: 10.1021/acscentsci.7b00550168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitF2gsrk%253D&md5=b606a11b4272d62ae4f7de4b7709d25aThe Matter Simulation (R)evolutionAspuru-Guzik, Alan; Lindh, Roland; Reiher, MarkusACS Central Science (2018), 4 (2), 144-152CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)To date, the program for the development of methods and models for atomistic and continuum simulation directed toward chems. and materials has reached an incredible degree of sophistication and maturity. Currently, one can witness an increasingly rapid emergence of advances in computing, artificial intelligence, and robotics. This drives us to consider the future of computer simulation of matter from the mol. to the human length and time scales in a radical way that deliberately dares to go beyond the foreseeable next steps in any given discipline. This perspective article presents a view on this future development that we believe is likely to become a reality during our lifetime.
- 169Matthews, D. Science goes virtual. Nature 2018, 557, 127– 128, DOI: 10.1038/d41586-018-04997-2There is no corresponding record for this reference.
- 170Cruz-Neira, C.; Sandin, D. J.; DeFanti, T. A. Surround-Screen Projection-Based Virtual Reality: The Design and Implementation of the CAVE. Proceedings of the 20th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, NY, USA, 1993; pp 135– 142.There is no corresponding record for this reference.
- 171Ai, Z.; Fröhlich, T. Molecular Dynamics Simulation in Virtual Environments. Comput. Graphics Forum 1998, 17, 267– 273, DOI: 10.1111/1467-8659.00273There is no corresponding record for this reference.
- 172Prins, J. F.; Hermans, J.; Mann, G.; Nyland, L. S.; Simons, M. A Virtual Environment for Steered Molecular Dynamics. Future Gener. Comp. Sy. 1999, 15, 485– 495, DOI: 10.1016/S0167-739X(99)00005-9There is no corresponding record for this reference.
- 173Ǩrenek, A. Haptic Rendering of Complex Force Fields. Proceedings of the Workshop on Virtual Environments 2003; ACM: New York, NY, USA, 2003; pp 231– 239.There is no corresponding record for this reference.
- 174Lee, Y.-G.; Lyons, K. W. Smoothing Haptic Interaction Using Molecular Force Calculations. Comput.-Aided Design 2004, 36, 75– 90, DOI: 10.1016/S0010-4485(03)00080-0There is no corresponding record for this reference.
- 175Morin, S.; Redon, S. A Force-Feedback Algorithm for Adaptive Articulated-Body Dynamics Simulation. IEEE International Conference on Robotics and Automation; IEEE, 2007; pp 3245– 3250.There is no corresponding record for this reference.
- 176Daunay, B.; Régnier, S. Stable Six Degrees of Freedom Haptic Feedback for Flexible Ligand-Protein Docking. Comput.-Aided Design 2009, 41, 886– 895, DOI: 10.1016/j.cad.2009.06.010There is no corresponding record for this reference.
- 177Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Haptic Feedback for Molecular Simulation. 2009 IEEE/RSJ. International Conference on Intelligent Robots and Systems; IEEE, 2009; pp 237– 242.There is no corresponding record for this reference.
- 178Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Comparing Position and Force Control for Interactive Molecular Simulators with Haptic Feedback. J. Mol. Graphics Modell. 2010, 29, 280– 289, DOI: 10.1016/j.jmgm.2010.06.003178https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFamtLvP&md5=8d81e29d4693725c0ada3ce7db0cebc0Comparing position and force control for interactive molecular simulators with haptic feedbackBolopion, Aude; Cagneau, Barthelemy; Redon, Stephane; Regnier, StephaneJournal of Molecular Graphics & Modelling (2010), 29 (2), 280-289CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)This paper presents a novel tool for the anal. of new mol. structures which enables a wide variety of manipulations. It is composed of a mol. simulator and a haptic device. The simulation software deals with systems of hundreds or thousands of degrees of freedom and computes the reconfiguration of the mols. in a few tenths of a second. For the ease of manipulation and to help the operator understand nanoscale phenomena, a haptic device is connected to the simulator. To handle a wide variety of applications, both position and force control are implemented. To our knowledge, this is the first time the applications of force control are detailed for mol. simulation. These two control modes are compared in terms of adequacy with mol. dynamics, transparency and stability sensitivity with respect to environmental conditions. Based on their specificity the operations they can realize are detailed. Expts. highlight the usability of our tool for the different steps of the anal. of mol. structures. It includes the global reconfiguration of a mol. system, the measurement of mol. properties and the comprehension of nanoscale interactions. Compared to most existing systems, the one developed in this paper offers a wide range of possible expts. The detailed anal. of the properties of the control modes can be easily used to implement haptic feedback on other mol. simulators.
- 179Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Haptic Molecular Simulation Based on Force Control. 2010 IEEE/ASME International Conference on Advanced Intelligent Mechatronics; IEEE, 2010; pp 329– 334.There is no corresponding record for this reference.
- 180Bolopion, A.; Cagneau, B.; Redon, S.; Régnier, S. Variable Gain Haptic Coupling for Molecular Simulation. 2011 IEEE World Haptics Conference; IEEE, 2011; pp 469– 474.There is no corresponding record for this reference.
- 181Durlach, N.; Mavor, A.; Development, C.; Board, C.; Council, N. Virtual Reality: Scientific and Technological Challenges; National Academies Press, 1994.There is no corresponding record for this reference.
- 182Mark, W. R.; Randolph, S. C.; Finch, M.; Van Verth, J. M.; Taylor, R. M., II. Adding Force Feedback to Graphics Systems: Issues and Solutions. Proceedings of the 23rd Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1996; pp 447– 452.There is no corresponding record for this reference.
- 183Ruspini, D. C.; Kolarov, K.; Khatib, O. The Haptic Display of Complex Graphical Environments. Proceedings of the 24th Annual Conference on Computer Graphics and Interactive Techniques; ACM: New York, 1997; pp 345– 352.There is no corresponding record for this reference.
- 184Cruz-Neira, C.; Langley, R.; Bash, P. VIBE: A Virtual Biomolecular Environment for Interactive Molecular Modeling. Comput. Chem. 1996, 20, 469– 477, DOI: 10.1016/0097-8485(96)00009-5184https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XlslWhu7Y%253D&md5=c1c2ca7665c30f7500d6b2e721dc29e0VIBE: a virtual biomolecular environment for interactive molecular modelingCruz-Neira, C.; Langley, R.; Bash, P. A.Computers & Chemistry (Oxford) (1996), 20 (4), 469-477CODEN: COCHDK; ISSN:0097-8485. (Elsevier)Virtual reality tightly coupled to high performance computing and communications ushers in a new era for the study of mol. recognition and the rational design of pharmaceutical compds. We have created a Virtual Biomol. Environment (VIBE), which consists of (1) massively parallel computing to simulate the phys. and chem. properties of a mol. system, (2) the Cave Automatic Virtual Environment (CAVE) for immersive display and interaction with the mol. system, and (3) a high-speed network interface to exchange data between the simulation and the CAVE. VIBE enables mol. scientists to have a visual, auditory, and haptic experience with a chem. system, while simultaneously manipulating its phys. properties by steering, in real-time, a simulation executed on a supercomputer. We demonstrate the characteristics of VIBE using a HIV protease-cyclic urea inhibitor complex.
- 185Férey, N.; Nelson, J.; Martin, C.; Picinali, L.; Bouyer, G.; Tek, A.; Bourdot, P.; Burkhardt, J.; Katz, B.; Ammi, M.; Etchebest, C.; Autin, L. Multisensory VR Interaction for Protein-Docking in the CoRSAIRe Project. Virtual Reality 2009, 13, 273– 293, DOI: 10.1007/s10055-009-0136-zThere is no corresponding record for this reference.
- 186Glowacki, D. R.; O’Connor, M.; Calabro, G.; Price, J.; Tew, P.; Mitchell, T.; Hyde, J.; Tew, D. P.; Coughtrie, D. J.; McIntosh-Smith, S. A GPU-Accelerated Immersive Audio-Visual Framework for Interaction with Molecular Dynamics Using Consumer Depth Sensors. Faraday Discuss. 2014, 169, 63– 87, DOI: 10.1039/C4FD00008KThere is no corresponding record for this reference.
- 187Arbon, R. E.; Jones, A. J.; Bratholm, L. A.; Mitchell, T.; Glowacki, D. R. Sonifying Stochastic Walks on Biomolecular Energy Landscapes. 2018, arXiv 1803.05805.There is no corresponding record for this reference.
- 188Ouh-young, M.; Pique, M.; Hughes, J.; Srinivasan, N.; Brooks, F. P. Using a Manipulator for Force Display in Molecular Docking. IEEE International Conference on Robotics and Automation; IEEE, 1988; pp 1824– 1829.There is no corresponding record for this reference.
- 189Brooks, F. P., Jr.; Ouh-Young, M.; Batter, J. J.; Jerome Kilpatrick, P. Project GROPE — Haptic Displays for Scientific Visualization. SIGGRAPH Comput. Graph. 1990, 24, 177– 185, DOI: 10.1145/97880.97899There is no corresponding record for this reference.
- 190Levine, D.; Facello, M.; Hallstrom, P.; Reeder, G.; Walenz, B.; Stevens, F. Stalk: An Interactive System for Virtual Molecular Docking. IEEE Comput. Sci. Eng. 1997, 4, 55– 65, DOI: 10.1109/99.609834190https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkslOksro%253D&md5=13346f7b2c9a5751e55e859fea6dc97dStalk: an interactive system for virtual molecular dockingLevine, David; Facello, Michael; Hallstrom, Philip; Reeder, Gregory; Walenz, Brian; Stevens, FredIEEE Computational Science & Engineering (1997), 4 (2), 55-65CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)Several recent technols., i.e., genetic algorithms, parallel and distributed computing, virtual reality, and high-speed networking, underlie a new approach to the computational study of how biomols. interact or dock together. With the Stalk system, a user in a virtual reality environment can interact with a genetic algorithm running on a parallel computer to help in the search for likely geometric configurations.
- 191Brooks, F. P., Jr. Impressions by a dinosaur. Faraday Discuss. 2014, 169, 521– 527, DOI: 10.1039/C4FD00130CThere is no corresponding record for this reference.
- 192O’Connor, M.; Deeks, H. M.; Dawn, E.; Metatla, O.; Roudaut, A.; Sutton, M.; Thomas, L. M.; Glowacki, B. R.; Sage, R.; Tew, P.; Wonnacott, M.; Bates, P.; Mulholland, A. J.; Glowacki, D. R. Sampling Molecular Conformations and Dynamics in a Multiuser Virtual Reality Framework. Sci. Adv. 2018, 4, eaat2731 DOI: 10.1126/sciadv.aat2731There is no corresponding record for this reference.
- 193Bayazit, O.; Song, G.; Amato, N. Ligand Binding with OBPRM and User Input. IEEE International Conference on Robotics and Automation; IEEE, 2001; pp 954– 959.There is no corresponding record for this reference.
- 194Nagata, H.; Mizushima, H.; Tanaka, H. Concept and Prototype of Protein-Ligand Docking Simulator with Force Feedback Technology. Bioinformatics 2002, 18, 140– 146, DOI: 10.1093/bioinformatics/18.1.140There is no corresponding record for this reference.
- 195Lai-Yuen, S. K.; Lee, Y.-S. Computer-Aided Molecular Design (CAMD) with Force-Torque Feedback. Ninth International Conference on Computer Aided Design and Computer Graphics; ACM: New York, 2005; pp 199– 204.There is no corresponding record for this reference.
- 196Birmanns, S.; Wriggers, W. Interactive Fitting Augmented by Force-Feedback and Virtual Reality. J. Struct. Biol. 2003, 144, 123– 131, DOI: 10.1016/j.jsb.2003.09.018There is no corresponding record for this reference.
- 197Wollacott, A. M.; Merz, K. M., Jr. Haptic Applications for Molecular Structure Manipulation. J. Mol. Graphics Modell. 2007, 25, 801– 805, DOI: 10.1016/j.jmgm.2006.07.005197https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsFOiu7w%253D&md5=53a6dc20d08d1a0de0cee9053589ddf9Haptic applications for molecular structure manipulationWollacott, Andrew M.; Merz, Kenneth M.Journal of Molecular Graphics & Modelling (2007), 25 (6), 801-805CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Inc.)We describe the application of haptic technol. to enhance the information available in chem. systems, specifically related to computational drug design. These methods are designed to build upon the visual information presented by mol. viewers and add the sensation of touch, or force feedback. The addn. of sensory input can aid in the anal. of mol. structures and the understanding of intermol. interactions by delivering chem. relevant forces to the end user.
- 198Subasi, E.; Basdogan, C. A New Haptic Interaction and Visualization Approach for Rigid Molecular Docking in Virtual Environments. Presence 2008, 17, 73– 90, DOI: 10.1162/pres.17.1.73There is no corresponding record for this reference.
- 199Heyd, J.; Birmanns, S. Immersive Structural Biology: A New Approach to Hybrid Modeling of Macromolecular Assemblies. Virtual Reality 2009, 13, 245– 255, DOI: 10.1007/s10055-009-0129-yThere is no corresponding record for this reference.
- 200Anthopoulos, A.; Pasqualetto, G.; Grimstead, I.; Brancale, A. Haptic-Driven, Interactive Drug Design: Implementing a GPU-Based Approach to Evaluate the Induced Fit Effect. Faraday Discuss. 2014, 169, 323– 342, DOI: 10.1039/C3FD00139C200https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jE&md5=baa69798111ce24fac6a771e906d262eHaptic-driven, interactive drug design: implementing a GPU-based approach to evaluate the induced fit effectAnthopoulos, Athanasios; Pasqualetto, Gaia; Grimstead, Ian; Brancale, AndreaFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 323-342CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)In this paper, we describe a hybrid meta-heuristics method of energy minimization and conformational sampling and its application into our haptic-driven mol. modeling simulator. The proposed method has been designed to suit real-time mol. docking simulations, where the time-lapse between two successive ligand poses is relatively small. In these situations, the energy minimization problem becomes increasingly complex and chaotic. The algorithm is tuned to take advantage of recent advances in GPU computing with asynchronous kernel execution, which has allowed us to include full protein flexibility in the real-time interactive, haptic-driven simulations. Finally, in this paper, we will also discuss the implementation of such high-performance computing approaches in our software, discussing the results of our initial validation studies, highlighting the advantages and limitations of such interactive methodol.
- 201Iakovou, G.; Hayward, S.; Laycock, S. D. A Real-Time Proximity Querying Algorithm for Haptic-Based Molecular Docking. Faraday Discuss. 2014, 169, 359– 377, DOI: 10.1039/C3FD00123G201https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7jP&md5=ba322c73d491c8d3218f2ec2e97f4a3fA real-time proximity querying algorithm for haptic-based molecular dockingIakovou, Georgios; Hayward, Steven; Laycock, StephenFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 359-377CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Intermol. binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacol. properties of drugs. Mol. docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the mols. to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calcn. of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calcns. must be performed within 1ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (esp. for large mols.), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermol. forces in real time. Our motivation is the eventual development of a haptic-based docking soln. that can model mol. flexibility. Uniquely in a haptics application we use octrees to decomp. the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calcns. are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large mol. structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, mol. docking application called Haptimol_RD. The user can use the haptic device to orientate the mols. in space, sense the interaction forces on the device, and guide the mols. to their binding pose. Haptimol_RD is designed to run on consumer level hardware, i.e. there is no need for specialized/proprietary hardware.
- 202Iakovou, G.; Hayward, S.; Laycock, S. D. Adaptive GPU-Accelerated Force Calculation for Interactive Rigid Molecular Docking Using Haptics. J. Mol. Graphics Modell. 2015, 61, 1– 12, DOI: 10.1016/j.jmgm.2015.06.003202https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtF2ksbzL&md5=fc7fcb1082a8e50b08323d4ab720b249Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using hapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Molecular Graphics & Modelling (2015), 61 (), 1-12CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)Mol. docking systems model and simulate in silico the interactions of intermol. binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch, but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500 Hz to 1 kHz. The authors present an adaptive force calcn. approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to mol. simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to det. the set of interat. interactions within a cutoff distance. The total force is then calcd. from this set. The approach can achieve force updates in <2 ms for mol. structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calcn. approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates.
- 203Iakovou, G.; Hayward, S.; Laycock, S. D. Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics. J. Chem. Inf. Model. 2017, 57, 1142– 1152, DOI: 10.1021/acs.jcim.7b00051203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmsVahs74%253D&md5=88a043fa234a92e12c81dfd453884b01Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with HapticsIakovou, Georgios; Hayward, Steven; Laycock, Stephen D.Journal of Chemical Information and Modeling (2017), 57 (5), 1142-1152CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Haptic technol. facilitates user interaction with the virtual world via the sense of touch. In mol. docking, haptics enables the user to sense the interaction forces during the docking process. Here the authors describe a haptics-assisted interactive software tool, called Haptimol_RD, for the study of docking interactions. By utilizing GPU-accelerated proximity querying methods very large systems can now be studied. Methods for force scaling, multipoint collision response and haptic navigation are described that address force stability issues that are particular to the interactive docking of large systems. Thus, Haptimol_RD expands, for the first time, the use of interactive biomol. haptics to the study of protein-protein interactions. Unlike existing approaches, Haptimol_RD is designed to run on relatively inexpensive consumer-level hardware and is freely available to the community.
- 204Izrailev, S.; Stepaniants, S.; Isralewitz, B.; Kosztin, D.; Lu, H.; Molnar, F.; Wriggers, W.; Schulten, K. In Computational Molecular Dynamics: Challenges, Methods, Ideas; Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A., Reich, S., Skeel, R., Eds.; Lecture Notes in Computational Science and Engineering; Springer: Berlin, Heidelberg, 1999; Vol. 4, pp 39– 65.There is no corresponding record for this reference.
- 205Grubmüller, H.; Heymann, B.; Tavan, P. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force. Science 1996, 271, 997– 999, DOI: 10.1126/science.271.5251.997205https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XhtFCru7g%253D&md5=8a013b443101d48aed80fcde1ec7d924Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture forceGrubmueller, Helmut; Heymann, Berthold; Tavan, PaulScience (Washington, D. C.) (1996), 271 (5251), 997-9CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The force required to rupture the streptavidin-biotin complex was calcd. here by computer simulations. The computed force agrees well with that obtained by recent single mol. at. force microscope expts. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, addnl. water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were obsd.
- 206Izrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K. Molecular Dynamics Study of Unbinding of the Avidin-Biotin Complex. Biophys. J. 1997, 72, 1568– 1581, DOI: 10.1016/S0006-3495(97)78804-0206https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitFeisbk%253D&md5=649ad913ebac2d1b320aebef229a8c50Molecular dynamics study of unbinding of the avidin-biotin complexIzrailev, S.; Stepaniants, S.; Balsera, M.; Oono, Y.; Schulten, K.Biophysical Journal (1997), 72 (4), 1568-1581CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)We report mol. dynamics simulations that induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force consts. close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force const. The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calcd. rupture forces exceed by far those obsd. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the assocd. Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM expts., and that simulated unbinding cannot be readily extrapolated to the exptl. obsd. rupture.
- 207Balsera, M.; Stepaniants, S.; Izrailev, S.; Oono, Y.; Schulten, K. Reconstructing Potential Energy Functions from Simulated Force-Induced Unbinding Processes. Biophys. J. 1997, 73, 1281– 1287, DOI: 10.1016/S0006-3495(97)78161-XThere is no corresponding record for this reference.
- 208Isralewitz, B.; Izrailev, S.; Schulten, K. Binding Pathway of Retinal to Bacterio-Opsin: A Prediction by Molecular Dynamics Simulations. Biophys. J. 1997, 73, 2972– 2979, DOI: 10.1016/S0006-3495(97)78326-7208https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXnsl2murc%253D&md5=ad6760df6b7abc856b68c31980e1da86Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulationsIsralewitz, Barry; Izrailev, Sergei; Schulten, KlausBiophysical Journal (1997), 73 (6), 2972-2979CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)Formation of bacteriorhodopsin (bR) from apoprotein and retinal has been studied exptl., but the actual pathway, including the point of entry, is little understood. Mol. dynamics simulations provide a surprisingly clear prediction. A window between bR helixes E and F in the transmembrane part of the protein can be identified as an entry point for retinal. Steered mol. dynamics, performed by applying a series of external forces in the range of 200-1000 pN over a period of 0.2 ns to retinal, allows one to ext. this chromophore from bR once the Schiff base bond to Lys216 is cleaved. Extn. proceeds until the retinal tail forms a hydrogen bond network with the Ala144, Met145, and Ser183 side groups lining the exit/entry window. The manipulation induces a distortion with a fitted root mean square deviation of coordinates (ignoring retinal, water, and hydrogen atoms) of less than 1.9 Å by the time the retinal carbonyl reaches the protein surface. The forces needed to ext. retinal are due to friction and do not indicate significant potential barriers. The simulations therefore suggest a pathway for the binding of retinal. Water mols. are found to play a crucial role in the binding process.
- 209Jarzynski, C. Nonequilibrium Equality for Free Energy Differences. Phys. Rev. Lett. 1997, 78, 2690, DOI: 10.1103/PhysRevLett.78.2690209https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXisVSrt7c%253D&md5=5e572f64b7e9044fff5af96867602877Nonequilibrium equality for free energy differencesJarzynski, C.Physical Review Letters (1997), 78 (14), 2690-2693CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)An expression is derived for the equil. free energy difference between two configurations of a system, in terms of an ensemble of finite-time measurements of the work performed in parametrically switching from one configuration to the other. Two well-known identities emerge as limiting cases of this result.
- 210Nelson, M.; Humphrey, W.; Kufrin, R.; Gursoy, A.; Dalke, A.; Kale, L.; Skeel, R.; Schulten, K. MDScope — a Visual Computing Environment for Structural Biology. Comput. Phys. Commun. 1995, 91, 111– 133, DOI: 10.1016/0010-4655(95)00045-H210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXps1Wrtrg%253D&md5=5581371fd83f3a501280347abd691318MDScope - a visual computing environment for structural biologyNelson, Mark; Humphrey, William; Kufrin, Richard; Gursoy, Attila; Dalke, Andrew; Kale, Laxmikant; Skeel, Robert; Schulten, KlausComputer Physics Communications (1995), 91 (1-3), 111-33CODEN: CPHCBZ; ISSN:0010-4655. (Elsevier)MDScope is an integrated set of computational tools which function as an interactive visual computing environment for the simulation and study of biopolymers. This environment consists of three parts: (1) vmd, a mol. visualization program for interactive display of mol. systems; (2) namd, a mol. dynamics program designed for performance, scalability, modularity, and portability, which runs in parallel on a variety of computer platforms; (3) MDComm, a protocol and library which functions as the unifying communication agent between the visualization and simulation components of MDScope. Namd is expressly designed for distributed memory parallel architectures and uses a spatial decompn. parallelization strategy coupled with a multi-threaded, message-driven computation model which reduces inefficiencies due to communication latency. Through the MDComm software, vmd acts as a graphical interface and interactive control for namd, allowing a user running namd to utilize a parallel platform for computational power while visualizing the trajectory as it is computed. Modularity in both vmd and namd is accomplished through an object-oriented design, which facilitates the addn. of features and new algorithms.
- 211Rapaport, D. Interactive Molecular Dynamics. Phys. A 1997, 240, 246– 254, DOI: 10.1016/S0378-4371(97)00148-9211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXkt1agtLo%253D&md5=8376a0d92a34d61102b994d2dea8e323Interactive molecular dynamicsRapaport, D. C.Physica A: Statistical and Theoretical Physics (Amsterdam) (1997), 240 (1-2), 246-254CODEN: PHYADX; ISSN:0378-4371. (Elsevier)We address the use of visualization and interactivity in mol. dynamics simulation. In an interactive environment the simulator is not only provided with the means to view the system in alternative ways in real-time, but is also able to 'steer' the computation in different directions by changing the governing parameters of the system. The simulational experience can be enhanced significantly by such means. Several examples are outlined.
- 212Rapaport, D. C. An Introduction to Interactive Molecular-Dynamics Simulations. Comput. Phys. 1997, 11, 337– 347, DOI: 10.1063/1.168612212https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmsVCiurs%253D&md5=dd6d05d9bec0be44a4f0deb1ea2828b8An introduction to interactive molecular-dynamics simulationsRapaport, D. C.Computers in Physics (1997), 11 (4), 337-347CODEN: CPHYE2; ISSN:0894-1866. (American Institute of Physics)A review with 8 refs.
- 213Leech, J.; Prins, J. F.; Hermans, J. SMD: Visual Steering of Molecular Dynamics for Protein Design. IEEE Comput. Sci. Eng. 1996, 3, 38– 45, DOI: 10.1109/99.556511213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXitlSqtQ%253D%253D&md5=6f7100b4048a22f1cdc0a43ab30048b4SMD: visual steering of molecular dynamics for protein designLeech, Jonathan; Prins, Jan F.; Hermans, JanIEEE Computational Science & Engineering (1996), 3 (4), 38-45CODEN: ISCEE4; ISSN:1070-9924. (IEEE Computer Society)SMD, a system for interactively steering mol. dynamics calcns. of protein mols., includes computation, visualization, and communications components. Biochemists can "tug" mols. into different shapes by specifying external forces in the graphical interface, which are added to internal forces representing at. bonds and nonbonded interactions.
- 214Vormoor, O. Quick and Easy Interactive Molecular Dynamics Using Java3D. Comput. Sci. Eng. 2001, 3, 98– 104, DOI: 10.1109/5992.947113214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFOjt7w%253D&md5=a5b57a2dc0a27f019479fdedba6a44a8Quick and easy interactive molecular dynamics using Java3DVormoor, OliverComputing in Science & Engineering (2001), 3 (5), 98-104CODEN: CSENFA; ISSN:1521-9615. (American Institute of Physics)An interactive mol. dynamics software, called Java Interactive Mol. Dynamics (JIMD), was developed for the study of colloid clusters. JIMD is not a stand-alone interactive mol. dynamic application, but a software package that can be quickly and easily adapted to existing mol. dynamics simulation software. For rendering the mol. system, JIMD uses Java3D, the application programing interface for writing 3D graphics applications in Java.
- 215Stone, J. E.; Gullingsrud, J.; Schulten, K. A System for Interactive Molecular Dynamics Simulation. Proceedings of the 2001 Symposium on Interactive 3D Graphics; ACM: New York, NY, USA, 2001; pp 191– 194.There is no corresponding record for this reference.
- 216Grayson, P.; Tajkhorshid, E.; Schulten, K. Mechanisms of Selectivity in Channels and Enzymes Studied with Interactive Molecular Dynamics. Biophys. J. 2003, 85, 36– 48, DOI: 10.1016/S0006-3495(03)74452-XThere is no corresponding record for this reference.
- 217Férey, N.; Delalande, O.; Grasseau, G.; Baaden, M. A VR Framework for Interacting with Molecular Simulations. Proceedings of the 2008 ACM Symposium on Virtual Reality Software and Technology; ACM: New York, NY, USA, 2008; pp 91– 94.There is no corresponding record for this reference.
- 218Dreher, M.; Piuzzi, M.; Turki, A.; Chavent, M.; Baaden, M.; Férey, N.; Limet, S.; Raffin, B.; Robert, S. Interactive Molecular Dynamics: Scaling up to Large Systems. Procedia Comput. Sci. 2013, 18, 20– 29, DOI: 10.1016/j.procs.2013.05.165There is no corresponding record for this reference.
- 219Dreher, M.; Prevoteau-Jonquet, J.; Trellet, M.; Piuzzi, M.; Baaden, M.; Raffin, B.; Ferey, N.; Robert, S.; Limet, S. ExaViz: A Flexible Framework to Analyse, Steer and Interact with Molecular Dynamics Simulations. Faraday Discuss. 2014, 169, 119– 142, DOI: 10.1039/C3FD00142CThere is no corresponding record for this reference.
- 220Stone, J. E.; Kohlmeyer, A.; Vandivort, K. L.; Schulten, K. In Advances in Visual Computing; Bebis, G., Boyle, R., Parvin, B., Koracin, D., Chung, R., Hammound, R., Hussain, M., Kar-Han, T., Crawfis, R., Thalmann, D., Kao, D., Avila, L., Eds.; Lecture Notes in Computer Science; Springer: Berlin, Heidelberg, 2010; Vol. 6454, pp 382– 393.There is no corresponding record for this reference.
- 221Luehr, N.; Jin, A. G. B.; Martínez, T. J. Ab Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs). J. Chem. Theory Comput. 2015, 11, 4536– 4544, DOI: 10.1021/acs.jctc.5b00419221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVeqtrzP&md5=9d5ff51b17633add948dbacc2c22958fAb Initio Interactive Molecular Dynamics on Graphical Processing Units (GPUs)Luehr, Nathan; Jin, Alex G. B.; Martinez, Todd J.Journal of Chemical Theory and Computation (2015), 11 (10), 4536-4544CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)A virtual mol. modeling kit is developed based on GPU-enabled interactive ab initio mol. dynamics (MD). The code uses the TeraChem and VMD programs with a modified IMD interface. Optimization of the GPU accelerated TeraChem program specifically for small mol. systems is discussed, and a robust multiple time step integrator is employed to accurately integrate strong user-supplied pulling forces. Smooth and responsive visualization techniques are developed to allow interactive manipulation at min. simulation rates below five MD steps per s. Representative calcns. at the Hartree-Fock level of theory are demonstrated for mol. systems contg. up to a few dozen atoms.
- 222Surles, M. C.; Richardson, J. S.; Richardson, D. C.; Brooks, F. P. Sculpting Proteins Interactively: Continual Energy Minimization Embedded in a Graphical Modeling System. Protein Sci. 1994, 3, 198– 210, DOI: 10.1002/pro.5560030205222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXktlSgt74%253D&md5=2138dd23c7212467e7fe17ab717eaa44Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling systemSurles, Mark C.; Richardson, Jane S.; Richardson, David C.; Brooks, Frederick P., Jr.Protein Science (1994), 3 (), 198-210CODEN: PRCIEI; ISSN:0961-8368.The authors describe a new paradigm for modeling proteins in interactive computer graphics systems - continual maintenance of a phys. valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance an all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond strengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specific springs. The graphical interface can show bad and(or) favorable contacts, and individual energy terms can be turned on or off to det. their effects and interactions. Sculpt finds a local min. of the total energy that satisfies all the constraints using an augmented Lagrange-multiplier method; calcn. time increases only linearly with the no. of atoms because the matrix of constraint gradients is sparse and banded. On a 100-MHz MIPs R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per s on a 20-residue fragment and 2 updates per s on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2-stranded β-ribbon into an approx. β-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and phys. realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and (2) they help the user understand how different energy terms interact to stabilize a given conformation. The Sculpt paradigm combines many of the best features of interactive graphical modeling, energy minimization, and actual phys. models, and the authors propose it as an esp. productive way to use current and future increases in computer speed.
- 223Hanwell, M. D.; Curtis, D. E.; Lonie, D. C.; Vandermeersch, T.; Zurek, E.; Hutchison, G. R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminf. 2012, 4, 17, DOI: 10.1186/1758-2946-4-17223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVGksLg%253D&md5=f10400f51db314afa780e99403ca748aAvogadro: an advanced semantic chemical editor, visualization, and analysis platformHanwell, Marcus D.; Curtis, Donald E.; Lonie, David C.; Vandermeersch, Tim; Zurek, Eva; Hutchison, Geoffrey R.Journal of Cheminformatics (2012), 4 (), 17CODEN: JCOHB3; ISSN:1758-2946. (Chemistry Central Ltd.)Background: The Avogadro project has developed an advanced mol. editor and visualizer designed for cross-platform use in computational chem., mol. modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building mol. structures, formatting input files, and analyzing output of a wide variety of computational chem. packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chem. data types. Results: The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chem., physics, materials science, and biol. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate mol. structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for mol. dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here. Conclusions: Avogadro offers a semantic chem. builder and platform for visualization and anal. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extg. chem. data from a wide variety of formats, including computational chem. output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in org. chem., inorg. complexes, drug design, materials, biomols., and simulations.
- 224NANO-D. INRIA, SAMSON Software, Version ∼0.5.0; http://www.samson-connect.net/, 2016 (Accessed: 09 February 2018).There is no corresponding record for this reference.
- 225Bosson, M.; Richard, C.; Plet, A.; Grudinin, S.; Redon, S. Interactive Quantum Chemistry: A Divide-and-Conquer ASED-MO Method. J. Comput. Chem. 2012, 33, 779– 790, DOI: 10.1002/jcc.22905225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xkt1Gksw%253D%253D&md5=892979e833f4d542fe8634c28157fd7eInteractive quantum chemistry: A divide-and-conquer ASED-MO methodBosson, Maeel; Richard, Caroline; Plet, Antoine; Grudinin, Sergei; Redon, StephaneJournal of Computational Chemistry (2012), 33 (7), 779-790CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present interactive quantum chem. simulation at the atom superposition and electron delocalization MO (ASED-MO) level of theory. Our method is based on the divide-and-conquer (D and C) approach, which we show is accurate and efficient for this non-self-consistent semiempirical theory. The method has a linear complexity in the no. of atoms, scales well with the no. of cores, and has a small prefactor. The time cost is completely controllable, as all steps are performed with direct algorithms, i.e., no iterative schemes are used. We discuss the errors induced by the D and C approach, first empirically on a few examples, and then via a theor. study of two toy models that can be anal. solved for any no. of atoms. Thanks to the precision and speed of the D and C approach, we are able to demonstrate interactive quantum chem. simulations for systems up to a few hundred atoms on a current multicore desktop computer. When drawing and editing mol. systems, interactive simulations provide immediate, intuitive feedback on chem. structures. As the no. of cores on personal computers increases, and larger and larger systems can be dealt with, we believe such interactive simulations-even at lower levels of theory-should thus prove most useful to effectively understand, design and prototype mols., devices and materials. © 2012 Wiley Periodicals, Inc.
- 226Rossi, R.; Isorce, M.; Morin, S.; Flocard, J.; Arumugam, K.; Crouzy, S.; Vivaudou, M.; Redon, S. Adaptive Torsion-Angle Quasi-Statics: A General Simulation Method with Applications to Protein Structure Analysis and Design. Bioinformatics 2007, 23, i408– i417, DOI: 10.1093/bioinformatics/btm191There is no corresponding record for this reference.
- 227Bosson, M.; Grudinin, S.; Bouju, X.; Redon, S. Interactive Physically-Based Structural Modeling of Hydrocarbon Systems. J. Comput. Phys. 2012, 231, 2581– 2598, DOI: 10.1016/j.jcp.2011.12.006227https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Ogsbw%253D&md5=597f128c081cf549f0ef8667d746861cInteractive physically-based structural modeling of hydrocarbon systemsBosson, Mael; Grudinin, Sergei; Bouju, Xavier; Redon, StephaneJournal of Computational Physics (2012), 231 (6), 2581-2598CODEN: JCTPAH; ISSN:0021-9991. (Elsevier Inc.)Hydrocarbon systems have been intensively studied via numerical methods, including electronic structure computations, mol. dynamics and Monte Carlo simulations. Typically, these methods require an initial structural model (at. positions and types, topol., etc.) that may be produced using scripts and/or modeling tools. For many systems, however, these building methods may be ineffective, as the user may have to specify the positions of numerous atoms while maintaining structural plausibility. In this paper, we present an interactive phys.-based modeling tool to construct structural models of hydrocarbon systems. As the user edits the geometry of the system, at. positions are also influenced by the Brenner potential, a well-known bond-order reactive potential. In order to be able to interactively edit systems contg. numerous atoms, we introduce a new adaptive simulation algorithm, as well as a novel algorithm to incrementally update the forces and the total potential energy based on the list of updated relative at. positions. The computational cost of the adaptive simulation algorithm depends on user-defined error thresholds, and our potential update algorithm depends linearly with the no. of updated bonds. This allows us to enable efficient phys.-based editing, since the computational cost is decoupled from the no. of atoms in the system. We show that our approach may be used to effectively build realistic models of hydrocarbon structures that would be difficult or impossible to produce using other tools.
- 228Bosson, M.; Grudinin, S.; Redon, S. Block-Adaptive Quantum Mechanics: An Adaptive Divide-and-Conquer Approach to Interactive Quantum Chemistry. J. Comput. Chem. 2013, 34, 492– 504, DOI: 10.1002/jcc.23157There is no corresponding record for this reference.
- 229Jaillet, L.; Artemova, S.; Redon, S. IM-UFF: Extending the Universal Force Field for Interactive Molecular Modeling. J. Mol. Graphics Modell. 2017, 77, 350– 362, DOI: 10.1016/j.jmgm.2017.08.023229https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFGht7zL&md5=d8a6e882b109aa01ac2ce81758ec234bIM-UFF: Extending the universal force field for interactive molecular modelingJaillet, Leonard; Artemova, Svetlana; Redon, StephaneJournal of Molecular Graphics & Modelling (2017), 77 (), 350-362CODEN: JMGMFI; ISSN:1093-3263. (Elsevier Ltd.)The universal force field (UFF) is a broadly applicable classical force field that contains parameters for almost every atom type of the periodic table. This force field is non-reactive, i.e. the topol. of the system under study is considered as fixed and no creation or breaking of covalent bonds is possible. This paper introduces interactive modeling-UFF (IM-UFF), an extension of UFF that combines the possibility to significantly modify mol. structures (as with reactive force fields) with a broad diversity of supported systems thanks to the universality of UFF. Such an extension lets the user easily build and edit mol. systems interactively while being guided by physics based inter-at. forces. This approach introduces weighted atom types and weighted bonds, used to update topologies and atom parameterizations at every time step of a simulation. IM-UFF has been evaluated on a large set of benchmarks and is proposed as a self-contained implementation integrated in a new module for the SAMSON software platform for computational nanoscience available at http://www.samson-connect.net.
- 230Disz, T.; Papka, M.; Stevens, R.; Pellegrino, M.; Taylor, V. Virtual Reality Visualization of Parallel Molecular Dynamics Simulation. Proceedings of High-Performance Computing 1995, 483– 487There is no corresponding record for this reference.
- 231Akkiraju, N.; Edelsbrunner, H.; Fu, P.; Qian, J. Viewing Geometric Protein Structures from inside a CAVE. IEEE Comput. Graph. Appl. 1996, 16, 58– 61, DOI: 10.1109/38.511855There is no corresponding record for this reference.
- 232Salvadori, A.; Del Frate, G.; Pagliai, M.; Mancini, G.; Barone, V. Immersive Virtual Reality in Computational Chemistry: Applications to the Analysis of QM and MM Data. Int. J. Quantum Chem. 2016, 116, 1731– 1746, DOI: 10.1002/qua.25207232https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFCrurnF&md5=bbfba250da95eba7fbd0583621fcb11dImmersive virtual reality in computational chemistry: Applications to the analysis of QM and MM dataSalvadori, Andrea; Del Frate, Gianluca; Pagliai, Marco; Mancini, Giordano; Barone, VincenzoInternational Journal of Quantum Chemistry (2016), 116 (22), 1731-1746CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)The role of Virtual Reality (VR) tools in mol. sciences is analyzed in this contribution through the presentation of the Caffeine software to the quantum chem. community. Caffeine, developed at Scuola Normale Superiore, is specifically tailored for mol. representation and data visualization with VR systems, such as VR theaters and helmets. Usefulness and advantages that can be gained by exploiting VR are here reported, considering few examples specifically selected to illustrate different level of theory and mol. representation.
- 233García-Hernández, R. J.; Kranzlmüller, D. Virtual Reality Toolset for Material Science: NOMAD VR Tools. Augmented Reality, Virtual Reality, and Computer Graphics . 2017; pp 309– 319.There is no corresponding record for this reference.
- 234Haase, H.; Strassner, J.; Dai, F. VR Techniques for the Investigation of Molecule Data. Computers & Graphics 1996, 20, 207– 217, DOI: 10.1016/0097-8493(95)00127-1There is no corresponding record for this reference.
- 235Sauer, C.; Hastings, W.; Okamura, A. M. Virtual Environment for Exploring Atomic Bonding. Proceedings of EuroHaptics 2004; International Design Foundation, 2004; pp 232– 239.There is no corresponding record for this reference.
- 236Norrby, M.; Grebner, C.; Eriksson, J.; Boström, J. Molecular Rift: Virtual Reality for Drug Designers. J. Chem. Inf. Model. 2015, 55, 2475– 2484, DOI: 10.1021/acs.jcim.5b00544236https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGjurrL&md5=9a206f1ec098ca25df4a6b81f217891fMolecular Rift: Virtual Reality for Drug DesignersNorrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Bostroem, JonasJournal of Chemical Information and Modeling (2015), 55 (11), 2475-2484CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate phys. presence in the real world-a virtual reality. This is relevant to drug discovery since mol. models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Mol. Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for std. input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Mol. Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chem. and education. Mol. Rift is open source and can be downloaded from GitHub.
- 237Harvey, E.; Gingold, C. Haptic Representation of the Atom. 2000 IEEE Conference on Information Visualization. An International Conference on Computer Visualization and Graphics; IEEE, 2000; pp 232– 235.There is no corresponding record for this reference.
- 238Comai, S.; Mazza, D. A Haptic-Enhanced System for Molecular Sensing. Human-Computer Interaction – INTERACT 2009; Springer, 2009; pp 493– 496.There is no corresponding record for this reference.
- 239Satoh, H.; Nukada, T.; Akahane, K.; Sato, M. Construction of Basic Haptic Systems for Feeling the Intermolecular Force in Molecular Models. J. Comput. Aided Chem. 2006, 7, 38– 47, DOI: 10.2751/jcac.7.38There is no corresponding record for this reference.
- 240Stocks, M. B.; Hayward, S.; Laycock, S. D. Interacting with the Biomolecular Solvent Accessible Surface via a Haptic Feedback Device. BMC Struct. Biol. 2009, 9, 69, DOI: 10.1186/1472-6807-9-69240https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjkvVegtw%253D%253D&md5=863ad1d411a653bccac4b93267584afbInteracting with the biomolecular solvent accessible surface via a haptic feedback deviceStocks Matthew B; Hayward Steven; Laycock Stephen DBMC structural biology (2009), 9 (), 69 ISSN:.BACKGROUND: From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. RESULTS: A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. CONCLUSION: By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk), one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water accessibility of the biomolecular surface that cannot be so easily attained using conventional molecular graphics software.
- 241Sankaranarayanan, G.; Weghorst, S.; Sanner, M.; Gillet, A.; Olson, A. Role of Haptics in Teaching Structural Molecular Biology. 11th Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems; IEEE, 2003; pp 363– 366.There is no corresponding record for this reference.
- 242Persson, P. B.; Cooper, M. D.; Tibell, L. A. E.; Ainsworth, S.; Ynnerman, A.; Jonsson, B. H. Designing and Evaluating a Haptic System for Biomolecular Education. 2007 IEEE Virtual Reality Conference; IEEE, 2007; pp 171– 178.There is no corresponding record for this reference.
- 243Sourina, O.; Torres, J.; Wang, J. In Transactions on Edutainment II; Pan, Z., Cheok, A. D., Müller, W., Rhalibi, A. E., Eds.; Springer: Berlin, Heidelberg, 2009; Chapter Visual Haptic-Based Biomolecular Docking and Its Applications in E-Learning, pp 105– 118.There is no corresponding record for this reference.
- 244Bivall, P.; Ainsworth, S.; Tibell, L. A. E. Do Haptic Representations Help Complex Molecular Learning?. Sci. Educ. 2011, 95, 700– 719, DOI: 10.1002/sce.20439There is no corresponding record for this reference.
- 245Chastine, J. W.; Zhu, Y.; Brooks, J. C.; Owen, G. S.; Harrison, R. W.; Weber, I. T. A Collaborative Multi-View Virtual Environment for Molecular Visualization and Modeling. Coordinated and Multiple Views in Exploratory Visualization; IEEE, 2005; pp 77– 84.There is no corresponding record for this reference.
- 246Nadan, T.; Haffegee, A.; Watson, K. Collaborative and Parallelized Immersive Molecular Docking. International Conference on Computational Science 2009, 5545, 737– 745, DOI: 10.1007/978-3-642-01973-9_82There is no corresponding record for this reference.
- 247Hou, X.; Sourina, O.; Klimenko, S. Visual Haptic-Based Collaborative Molecular Docking. IFMBE Proceedings 2014, 43, 360– 363, DOI: 10.1007/978-3-319-02913-9_92There is no corresponding record for this reference.
- 248Davies, E.; Tew, P.; Glowacki, D.; Smith, J.; Mitchell, T. Evolutionary and Biologically Inspired Music, Sound, Art and Design. Proceedings of the 5th International Conference, EvoMUSART 2016, Porto, Portugal, March 30 – April 1, 2016; Johnson, C., Ciesielski, V., Correia, J. a., Machado, P., Eds.; Springer International Publishing, 2016; pp 17– 30.There is no corresponding record for this reference.
- 249Mitchell, T.; Hyde, J.; Tew, P.; Glowacki, D. R. Danceroom Spectroscopy: At the Frontiers of Physics, Performance, Interactive Art and Technology. Leonardo 2016, 49, 138– 147, DOI: 10.1162/LEON_a_00924There is no corresponding record for this reference.
- 250Marti, K. H.; Reiher, M. Haptic Quantum Chemistry. J. Comput. Chem. 2009, 30, 2010– 2020, DOI: 10.1002/jcc.21201250https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXptleqsLw%253D&md5=a0b7305f8d60a1b2a5c8bf5938d6f2a5Haptic quantum chemistryMarti, Konrad H.; Reiher, MarkusJournal of Computational Chemistry (2009), 30 (13), 2010-2020CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)We present an implementation designed to phys. experience quantum mech. forces between reactants in chem. reactions. This allows one to screen the profile of potential energy surfaces for the study of reaction mechanisms. For this, we have developed a interface between the user and a virtual lab. by means of a force-feedback haptic device. Potential energy surfaces of chem. reactions can be explored efficiently by rendering in the haptic device the gradients calcd. with first-principles methods. The underlying potential energy surface is accurately fitted on the fly by the interpolating moving least-squares (IMLS) scheme to a grid of quantum chem. electronic energies (and geometric gradients). In addn., we introduce a new IMLS-based method to locate min.-energy paths between two points on a potential energy surface. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009.
- 251Haag, M. P.; Marti, K. H.; Reiher, M. Generation of Potential Energy Surfaces in High Dimensions and Their Haptic Exploration. ChemPhysChem 2011, 12, 3204– 3213, DOI: 10.1002/cphc.201100539251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFKrtLjL&md5=df3aa356658e41578110e6b4dd5228aaGeneration of Potential Energy Surfaces in High Dimensions and Their Haptic ExplorationHaag, Moritz P.; Marti, Konrad H.; Reiher, MarkusChemPhysChem (2011), 12 (17), 3204-3213CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)A method is proposed for the automated generation of potential energy surfaces in high dimensions. It combines the existing algorithm for the definition of new energy data points, based on the interpolating moving least-squares algorithm with a simulated annealing procedure. This method is then studied in a haptic quantum chem. environment that requires a fast evaluation of gradients on a potential energy surface with automatic improvement of its accuracy. As an example we investigate the nitrogen binding pathway in the Schrock dinitrogen fixation complex with this set-up.
- 252Haag, M. P.; Reiher, M. Real-Time Quantum Chemistry. Int. J. Quantum Chem. 2013, 113, 8– 20, DOI: 10.1002/qua.24336252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVykt7fP&md5=ec7746303ee168218745cb0b4539fdb9Real-time quantum chemistryHaag, Moritz P.; Reiher, MarkusInternational Journal of Quantum Chemistry (2013), 113 (1), 8-20CODEN: IJQCB2; ISSN:0020-7608. (John Wiley & Sons, Inc.)Significant progress in the development of efficient and fast algorithms for quantum chem. calcns. has been made in the past two decades. The main focus has always been the desire to be able to treat ever larger mols. or mol. assemblies-esp. linear and sublinear scaling techniques are devoted to the accomplishment of this goal. However, as many chem. reactions are rather local, they usually involve only a limited no. of atoms so that models of about 200 (or even less) atoms embedded in a suitable environment are sufficient to study their mechanisms. Thus, the system size does not need to be enlarged, but remains const. for reactions of this type that can be described by less than 200 atoms. The question then arises how fast one can obtain the quantum chem. results. This question is not directly answered by linear-scaling techniques. In fact, ideas such as haptic quantum chem. (HQC) or interactive quantum chem. require an immediate provision of quantum chem. information which demands the calcn. of data in "real time." In this perspective, we aim at a definition of real-time quantum chem., explore its realm and eventually discuss applications in the field of HQC. For the latter, we elaborate whether a direct approach is possible by virtue of real-time quantum chem. © 2012 Wiley Periodicals, Inc.
- 253Haag, M. P.; Reiher, M. Studying Chemical Reactivity in a Virtual Environment. Faraday Discuss. 2014, 169, 89– 118, DOI: 10.1039/C4FD00021H253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7nF&md5=8b0b85c38bb608e1d9b8b6fa79ef8760Studying chemical reactivity in a virtual environmentHaag, Moritz P.; Reiher, MarkusFaraday Discussions (2014), 169 (Molecular Simulations and Visualization), 89-118CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Chem. reactivity of a set of reactants is detd. by its potential (electronic) energy (hyper)surface. The high dimensionality of this surface renders it difficult to efficiently explore reactivity in a large reactive system. Exhaustive sampling techniques and search algorithms are not straightforward to employ as it is not clear which explored path will eventually produce the min. energy path of a reaction passing through a transition structure. Here, the chemist's intuition would be of invaluable help, but it cannot be easily exploited because (1) no intuitive and direct tool for the scientist to manipulate mol. structures is currently available and because (2) quantum chem. calcns. are inherently expensive in terms of computational effort. In this work, we elaborate on how the chemist can be reintroduced into the exploratory process within a virtual environment that provides immediate feedback and intuitive tools to manipulate a reactive system. We work out in detail how this immersion should take place. We provide an anal. of modern semi-empirical methods which already today are candidates for the interactive study of chem. reactivity. Implications of manual structure manipulations for their phys. meaning and chem. relevance are carefully analyzed in order to provide sound theor. foundations for the interpretation of the interactive reactivity exploration.
- 254Haag, M. P.; Vaucher, A. C.; Bosson, M.; Redon, S.; Reiher, M. Interactive Chemical Reactivity Exploration. ChemPhysChem 2014, 15, 3301– 3319, DOI: 10.1002/cphc.201402342254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFSgsrnM&md5=5c26a58bb25aa70f7a71ebf0c93ea3ccInteractive Chemical Reactivity ExplorationHaag, Moritz P.; Vaucher, Alain C.; Bosson, Mael; Redon, Stephane; Reiher, MarkusChemPhysChem (2014), 15 (15), 3301-3319CODEN: CPCHFT; ISSN:1439-4235. (Wiley-VCH Verlag GmbH & Co. KGaA)Elucidating chem. reactivity in complex mol. assemblies of a few hundred atoms is, despite the remarkable progress in quantum chem., still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chem. reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mech. response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which tech. difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the SAMSON programming environment.
- 255Mühlbach, A. H.; Vaucher, A. C.; Reiher, M. Accelerating Wave Function Convergence in Interactive Quantum Chemical Reactivity Studies. J. Chem. Theory Comput. 2016, 12, 1228– 1235, DOI: 10.1021/acs.jctc.5b01156There is no corresponding record for this reference.
- 256Atsumi, T.; Nakai, H. Molecular Orbital Propagation to Accelerate Self-Consistent-Field Convergence in an Ab Initio Molecular Dynamics Simulation. J. Chem. Phys. 2008, 128, 094101, DOI: 10.1063/1.2839857256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjtl2qt74%253D&md5=1b02d7ccbc0390afd6bc6421fe3d2f36Molecular orbital propagation to accelerate self-consistent-field convergence in an ab initio molecular dynamics simulationAtsumi, Teruo; Nakai, HiromiJournal of Chemical Physics (2008), 128 (9), 094101/1-094101/9CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)Based on the idea of MO propagation, we propose a novel effective method for predicting initial guesses for the self-consistent-field calcns. in direct ab initio mol. dynamics (AIMD) simulations. This method, called LIMO, adopts the Lagrange interpolation (LI) polynomial technique and predicts initial MO coeffs. at the next AIMD step by using several previous results. Taking into account the crossing and/or mixing of MOs leads to orbital invariant formulas for the LIMO method. We also propose a simple method for detg. the optimal degree of the LI polynomial, which corresponds to the no. of previous steps. Numerical tests confirm that this proposed method is both effective and feasible. (c) 2008 American Institute of Physics.
- 257Atsumi, T.; Nakai, H. Acceleration of Self-Consistent-Field Convergence in Ab Initio Molecular Dynamics and Monte Carlo Simulations and Geometry Optimization. Chem. Phys. Lett. 2010, 490, 102– 108, DOI: 10.1016/j.cplett.2010.03.012257https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkt1ygt74%253D&md5=378feecb4e22a46ab096a8c43c0e5a9eAcceleration of self-consistent-field convergence in ab initio molecular dynamics and Monte Carlo simulations and geometry optimizationAtsumi, Teruo; Nakai, HiromiChemical Physics Letters (2010), 490 (1-3), 102-108CODEN: CHPLBC; ISSN:0009-2614. (Elsevier B.V.)We propose a novel acceleration method for self-consistent-field calcns. in direct ab initio mol. dynamics/Monte Carlo (AIMD/AIMC) simulations and geometry optimization. This acceleration method, so-called LSMO, predicts an initial guess of MOs (MOs) for the next simulation step by using the geometric information with the least-squares technique. Numerical tests confirm that the LSMO method is both effective and feasible in the AIMD/AIMC simulations and geometry optimization.
- 258Vaucher, A. C.; Haag, M. P.; Reiher, M. Real-Time Feedback from Iterative Electronic Structure Calculations. J. Comput. Chem. 2016, 37, 805– 812, DOI: 10.1002/jcc.24268258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVCltLrK&md5=847dceab1dfd98f653c508db8961b9adReal-time feedback from iterative electronic structure calculationsVaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Computational Chemistry (2016), 37 (9), 805-812CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)Real-time feedback from iterative electronic structure calcns. requires to mediate between the inherently unpredictable execution times of the iterative algorithm used and the necessity to provide data in fixed and short time intervals for real-time rendering. We introduce the concept of a mediator as a component able to deal with infrequent and unpredictable ref. data to generate reliable feedback. In the context of real-time quantum chem., the mediator takes the form of a surrogate potential that has the same local shape as the first-principles potential and can be evaluated efficiently to deliver at. forces as real-time feedback. The surrogate potential is updated continuously by electronic structure calcns. and guarantees to provide a reliable response to the operator for any mol. structure. To demonstrate the application of iterative electronic structure methods in real-time reactivity exploration, we implement self-consistent semiempirical methods as the data source and apply the surrogate-potential mediator to deliver reliable real-time feedback. © 2015 Wiley Periodicals, Inc.
- 259Vaucher, A. C.; Reiher, M. Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower Energy. J. Chem. Theory Comput. 2017, 13, 1219– 1228, DOI: 10.1021/acs.jctc.7b00011259https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivVKqs78%253D&md5=94b5a248bcc23b8c0d0e71e82c8be2f1Steering Orbital Optimization out of Local Minima and Saddle Points Toward Lower EnergyVaucher, Alain C.; Reiher, MarkusJournal of Chemical Theory and Computation (2017), 13 (3), 1219-1228CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)The general procedure underlying Hartree-Fock and Kohn-Sham d. functional theory calcns. consists in optimizing orbitals for a self-consistent soln. of the Roothaan-Hall equations in an iterative process. It is often ignored that multiple self-consistent solns. can exist, several of which may correspond to min. of the energy functional. In addn. to the difficulty sometimes encountered to converge the calcn. to a self-consistent soln., one must ensure that the correct self-consistent soln. was found, typically the one with the lowest electronic energy. Convergence to an unwanted soln. is in general not trivial to detect and will deliver incorrect energy and mol. properties and accordingly a misleading description of chem. reactivity. Wrong conclusions based on incorrect SCF convergence are particularly cumbersome in automated calcns. met in high-throughput virtual screening, structure optimizations, ab initio mol. dynamics, and in real-time explorations of chem. reactivity, where the vast amt. of data can hardly be manually inspected. Here, we introduce a fast and automated approach to detect and cure incorrect orbital convergence, which is esp. suited for electronic structure calcns. on sequences of mol. structures. Our approach consists of a randomized perturbation of the converged electron d. (matrix) intended to push orbital convergence to solns. that correspond to another stationary point (of potentially lower electronic energy) in the variational parameter space of an electronic wave function approxn.
- 260Vaucher, A. C.; Reiher, M. Molecular Propensity as a Driver for Explorative Reactivity Studies. J. Chem. Inf. Model. 2016, 56, 1470– 1478, DOI: 10.1021/acs.jcim.6b00264260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xht1WntbrN&md5=ba5071e8f71e85291382737cf389899aMolecular Propensity as a Driver for Explorative Reactivity StudiesVaucher, Alain C.; Reiher, MarkusJournal of Chemical Information and Modeling (2016), 56 (8), 1470-1478CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Quantum chem. studies of reactivity involve calcns. on a large no. of mol. structures and the comparison of their energies. Already the setup of these calcns. limits the scope of the results that one will obtain, because several system-specific variables such as the charge and spin need to be set prior to the calcn. For a reliable exploration of reaction mechanisms, a considerable no. of calcns. with varying global parameters must be taken into account, or important facts about the reactivity of the system under consideration can remain undetected. For example, one could miss crossings of potential energy surfaces for different spin states or might not note that a mol. is prone to oxidn. Here, we introduce the concept of mol. propensity to account for the predisposition of a mol. system to react across different electronic states in certain nuclear configurations or with other reactants present in the reaction liquor. Within our real-time quantum chem. framework, we developed an algorithm that automatically detects and flags such a propensity of a system under consideration.
- 261Heuer, M. A.; Vaucher, A. C.; Haag, M. P.; Reiher, M. Integrated Reaction Path Processing from Sampled Structure Sequences. J. Chem. Theory Comput. 2018, 14, 2052– 2062, DOI: 10.1021/acs.jctc.8b00019261https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXktFWgs78%253D&md5=aa7c203a39a0cc9c876174b2c517e4c5Integrated Reaction Path Processing from Sampled Structure SequencesHeuer, Michael A.; Vaucher, Alain C.; Haag, Moritz P.; Reiher, MarkusJournal of Chemical Theory and Computation (2018), 14 (4), 2052-2062CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)Sampled structure sequences obtained, for instance, from real-time reactivity explorations or first-principles mol. dynamics simulations contain valuable information about chem. reactivity. Eventually, such sequences allow for the construction of reaction networks that are required for the kinetic anal. of chem. systems. For this purpose, however, the sampled information must be processed to obtain stable chem. structures and assocd. transition states. The manual extn. of valuable information from such reaction paths is straightforward but unfeasible for large and complex reaction networks. For real-time quantum chem., this implies automatization of the extn. and relaxation process while maintaining immersion in the virtual chem. environment. Here, we describe an efficient path processing scheme for the on-the-fly construction of an exploration network by approximating the explored paths as continuous basis-spline curves.
- 262Reiher, M.; SCINE – Software for Chemical Interaction Networks. http://scine.ethz.ch (Accessed: 12. September 2018).There is no corresponding record for this reference.
