Transition State Conformers#
过渡状态符合者#
After we successfully searched for a TS with NEB-TS, we should consider its conformational flexibility via a fully automatic conformer search with GOAT.
This is important as the conformation of the TS structure can influence the resulting reaction barrier significantly. Often, the TS is even more affected than minimum structures of the reactants and products
due to the sterically crowded situation of adjacent substituents and ligands.
在我们使用 NEB-TS 成功搜索到 TS后，我们应该通过使用GOAT进行全自动构象异构体搜索来考虑其构象灵活性。这很重要，因为 TS 结构的构象可以显着影响所得的反应势垒。通常，由于相邻取代基和配体的空间拥挤情况，TS 比反应物和产物的最小结构受到的影响更大。
Figure: Schematic energy diagram of the conformational space of reactant, TS, and product.
图：反应物、TS和产物的构象空间示意图。#
Per default, GOAT would search for the relaxed global minimum structures and respective conformers. For a TS conformer search, we typically want to keep the atoms fixed that are directly
involved in the chemical transformation. To do so, we can use the constraint functionality within ORCA to modify our GOAT procedure.
默认情况下，GOAT 将搜索宽松的全局最小结构和相应的构象异构体。对于 TS 构象异构体搜索，我们通常希望保持直接参与化学转化的原子固定。为此，我们可以使用 ORCA 中的约束功能来修改我们的 GOAT 过程。
!XTB GOAT
%GEOM
Constraints
{C 0 C} # Constrain Cartesian coordinate of atom 0
{B 0 1 C} # Constrain bond of atoms 0 and 1
{A 0 1 2 C } # Constrain angle between atoms 0, 1, and 2
{D 0 1 2 3 C } # Constrain dihedral angle between atoms 0, 1, 2, and 3
END
END
*XYZFILE 0 1 ts.xyz
Warning 警告
Note, that ORCA starts counting at 0! Therefore, the first atom in your XYZ file will be atom 0.
请注意，ORCA 从 0 开始计数！因此，XYZ 文件中的第一个原子将是原子 0。
Example: Olefin Metathesis#
示例：烯烃复分解#
In this example, we will search for conformers of the transition state of a olefin metathesis reaction by a Schrock metathesis catalyst.
在此示例中，我们将搜索 Schrock 复分解催化剂进行的烯烃复分解反应过渡态的构象异构体。
Figure: TS of an olefin metathesis at a Schrock catalyst. Hydrogens are omitted for clarity.
图：Schrock 催化剂下烯烃复分解反应的 TS。为了清楚起见，省略了氢。#
The transition state of this reaction was found and optimized using the NEB-TS procedure with the GFN2-xTB method. In this case, the important atoms that are involved
in our reaction are the central molybdenum and the adjacent carbon atoms of the previous carbene ligand and the attacking alkene. We could also also include the
使用NEB-TS 程序和 GFN2-xTB 方法发现并优化了该反应的过渡态。在这种情况下，参与我们反应的重要原子是中心钼以及先前卡宾配体和攻击烯烃的相邻碳原子。我们还可以包括
!XTB GOAT
%PAL
NPROCS 16
END
%GEOM
Constraints
{ C 0 C }
{ C 1 C }
{ C 2 C }
END
END
*XYZFILE 0 1 ts.xyz
Note 笔记
Note, that we increased the number of processing cores to 16 to benefit from the high parallelity of the GOAT approach. Conformational searches for large, flexible molecules can be
very time consuming. Therefore, a combination of fast semi-empirical methods like GFN2-xTB and an increased number of cores is recommended.
请注意，我们将处理核心的数量增加到 16 个，以受益于 GOAT 方法的高并行性。对大而灵活的分子进行构象搜索可能非常耗时。因此，建议将 GFN2-xTB 等快速半经验方法与增加内核数量相结合。
We now run the GOAT conformer search with constrained Cartesian coordinates of the respective atoms Mo0, C1, and C2. After a successful GOAT run, it will give us a list of generated conformers ordered
by increasing energy with respect to the newly found global minimum structure.
现在，我们使用相应原子 Mo0、C1 和 C2 的约束笛卡尔坐标运行 GOAT 构象异构体搜索。成功运行 GOAT 后，它将为我们提供一份生成的构象异构体列表，这些构象异构体通过相对于新发现的全局最小结构增加能量来排序。
Global minimum found!
Writing structure to orca.globalminimum.xyz
# Final ensemble info #
Conformer Energy Degen. % total % cumul.
(kcal/mol)
------------------------------------------------------
0 0.000 1 24.18 24.18
1 0.390 1 12.52 36.70
2 0.440 1 11.51 48.21
3 0.457 1 11.18 59.40
4 0.595 1 8.86 68.26
5 0.743 1 6.90 75.15
6 0.838 1 5.88 81.03
7 1.007 1 4.42 85.45
8 1.186 1 3.26 88.72
9 1.423 1 2.19 90.91
10 1.640 1 1.52 92.43
11 1.649 1 1.50 93.92
12 1.867 1 1.03 94.96
13 2.105 1 0.69 95.65
14 2.205 1 0.59 96.23
[...]
Important 重要的
As we employed constraints in our GOAT run, the produced conformers are no fully optimized transition state structures! In any case, they should be finally optimized using the OptTS keyword.
This will also influence the energetic ranking. In general, the conformer ensemble should be refined afterwards using more accurate DFT or WFT methods to obtain more reliable results.
由于我们在 GOAT 运行中采用了约束，产生的构象异构体并不是完全优化的过渡态结构！无论如何，它们最终应该使用OptTS关键字进行优化。这也会影响能量排名。一般来说，随后应使用更准确的 DFT 或 WFT 方法对构象异构体集成进行细化，以获得更可靠的结果。
We can now visualize a selection of generated conformers that are stored in the basename.finalensemble.xyz file, and we see that the constrained atoms were perfectly kept in place during the GOAT run.
现在，我们可以可视化存储在basename.finalensemble.xyz文件中的一系列生成的构象异构体，并且我们看到受约束的原子在 GOAT 运行期间完美地保持在适当的位置。
Figure: a) Overlay of selected conformers. b) Structures of selected conformers with their respective relative energies in kcal·mol-1.
图：a) 选定构象异构体的叠加。 b) 所选构象异构体的结构及其各自的相对能量（kcal·mol -1 ） 。#
If we compare the energy of the yet unoptimized transition state conformers from our GOAT run with that of the input TS, we see that the new global minimum structure is 6.44 kcal·mol-1 lower
in energy even without further optimization! The respective absolute energies can be found in the second lines of the basename.xyz (starting structure) and the basename.globalminimum.xyz files.
如果我们将 GOAT 运行中尚未优化的过渡态构象异构体的能量与输入 TS 的能量进行比较，我们会发现，即使没有进一步优化，新的全局最小结构的能量也低了 6.44 kcal·mol -1 ！各自的绝对能量可以在basename.xyz （起始结构）和basename.globalminimum.xyz文件的第二行中找到。
Structures# 结构#
Input TS 输入传输流
93
Mo 0.06370 -0.28863 0.17017
C 0.84164 1.72537 0.43582
C 1.52344 0.27689 -1.34600
N -1.30128 0.25044 -0.75171
H -0.26969 -1.66376 -2.17422
H -0.65136 -2.81825 -3.45835
O -0.13617 -0.25848 2.24034
O 0.24700 -2.21112 0.37092
C 0.29419 -3.38192 1.05902
C -0.87377 0.21756 3.27512
C 0.73152 -4.53803 0.11457
C 1.24180 -3.35491 2.26679
C -1.16124 -3.71156 1.51808
C -0.62468 -0.73377 4.47753
C -0.33212 1.61191 3.70153
C -2.38966 0.31326 3.01714
F 0.67837 -0.84486 4.76724
F -1.24454 -0.36792 5.60296
F -1.05256 -1.97058 4.20136
F 0.99985 1.62713 3.79032
F -0.67075 2.56002 2.81769
F -0.80967 2.02886 4.88113
F 2.05670 -4.54676 -0.07838
F 0.42022 -5.73790 0.61587
F 0.17337 -4.44442 -1.09317
F -1.85881 -4.38139 0.59326
F -1.22045 -4.43558 2.63398
F -1.83646 -2.57517 1.73710
H 2.26257 -3.19419 1.92236
H 0.95694 -2.53229 2.91766
H 1.18788 -4.28984 2.81931
H -2.95262 -0.12159 3.83922
H -2.69463 1.34778 2.89170
H -2.60955 -0.23578 2.10094
C -2.30522 0.64608 -1.56169
C -2.31329 -1.58274 -2.87226
C -2.75620 2.63558 -0.04011
C -2.96097 1.88302 -1.33234
C -3.85714 2.37242 -2.26668
H -4.33254 3.32585 -2.09507
C -4.15679 1.66152 -3.41221
H -4.83839 2.06440 -4.14567
C -3.61326 0.40151 -3.58016
H -3.90384 -0.18780 -4.43836
C -2.71552 -0.13773 -2.67274
H -2.84186 -1.93794 -3.76512
C -0.82057 -1.80188 -3.10903
C -2.79413 -2.41636 -1.68345
C -4.06179 2.62612 0.76321
H -1.98947 2.10961 0.53954
C -2.29648 4.07621 -0.27085
H -4.39467 1.60668 0.94350
H -3.91592 3.12527 1.71875
H -4.84819 3.14963 0.22481
H -3.09495 4.67580 -0.70105
H -2.00545 4.52545 0.67577
H -1.44668 4.10489 -0.94580
H -3.87192 -2.32720 -1.56684
H -2.54386 -3.46388 -1.83112
H -2.31650 -2.06604 -0.76688
H -0.44616 -1.10623 -3.85768
C 2.90286 -0.41337 -1.43789
H 1.11942 0.27361 -2.36973
C 4.99218 -0.19037 0.01947
C 2.72448 -1.89144 -1.82100
C 3.72866 0.24932 -2.55423
H 1.79980 -0.67614 1.01812
H 5.60296 -0.06676 -0.85992
H 2.32668 -1.97495 -2.83053
H 3.67714 -2.41650 -1.78103
H 2.03568 -2.38298 -1.13777
H 4.02883 1.25820 -2.28477
H 4.61939 -0.33310 -2.77684
H 3.13481 0.30194 -3.46420
C 3.61561 -0.36095 -0.09696
C 2.88995 -0.53016 1.07701
C 3.49166 -0.50057 2.32164
H 2.89321 -0.60913 3.21405
C 4.86110 -0.31730 2.41675
H 5.33886 -0.28974 3.38379
C 5.60582 -0.16932 1.26054
H 6.67517 -0.03056 1.32166
C 1.64388 1.74157 -0.87132
H 0.16714 2.58408 0.46987
H 1.52579 1.85802 1.28502
C 1.08544 2.72374 -1.90384
H 2.69155 2.00572 -0.68020
H 1.53608 2.51791 -2.87835
H 0.00676 2.55991 -1.99439
C 1.37514 4.17570 -1.53620
H 2.44819 4.35624 -1.53117
H 0.91955 4.85121 -2.25671
H 0.98893 4.41339 -0.54860