High-accuracy computation of reaction barriers in enzymes
High-accuracy computation of reaction barriers in enzymes
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DOI：
10.1002/anie.200602711
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Werner, Hans-Joachim
中科院分区：
文献类型：
--
作者：
Claeyssens, Frederik;Harvey, Jeremy N.;Werner, Hans-Joachim
分别用B3LYP/6-31G*/CHARMM[1]和B3LYP/TZVP/GROMOS[2]对CM(16个通道)和PHBH(10个通道)的过渡态和相应的反应物进行了QM/MM几何优化。QM区域用Jaguar[3]和Turomole[4]处理，QM/MM耦合用QOMMMa[5]和ChemShell处理，CM和PHBH分别用[6]处理。最终的单点B3LYP、LMP2和LCCSD(T)计算是用从头算程序的MOLPRO程序包进行的。[7]对于CM，初始几何构型是从限制在过渡态区域的枯草杆菌CM的AM1/CHARMM[8，9]和PM3/CHARMM[10]QM/MM分子动力学(MD)模拟中获得的(详情见[11，12])。以C-O键断裂和C-C键形成之间的长度差作为反应坐标，通过绝热映射得到反应路径，对于PHBH，GROMOS和AM1/GROMOS MD运行的快照作为AM1/GROMOS几何构型优化的起始结构。得到的AM1/GROMOS过渡结构在B3LYP/GROMOS水平上通过重新优化QM区域和周围5？范围内的所有残基进行了优化。然后，通过仔细的逐步能量最小化，B3LYP/GROMOS过渡结构向缔合的反应物松弛，确保它们通过连续的路径连接。这里使用的映射坐标是断裂的O-O键和形成的C-O键之间的长度差。无花果。S1显示出活性中心内过渡态的优化结构，转移羟基部分与Pro 293的主链羰基之间存在氢键。
QM/MM geometry optimisations of transition states and corresponding reactants were performed using B3LYP/6-31G*/CHARMM [1] and B3LYP/TZVP/GROMOS [2] for CM (16 pathways) and PHBH (10 pathways) respectively. The QM regions were treated by Jaguar[3] and Turbomole [4], and the QM/MM coupling by QoMMMa[5] and ChemShell,[6] for CM and PHBH respectively. The final single-point B3LYP, LMP2, and LCCSD (T) calculations were carried out with the MOLPRO package of ab initio programs.[7] For CM, the initial geometries were sampled from AM1/CHARMM[8, 9] and PM3/CHARMM [10] QM/MM molecular dynamics (MD) simulations of Bacillus subtilis CM restrained to the transition state region (for details see[11, 12]). Reaction pathways were obtained by adiabatic mapping, using as a reaction coordinate the difference in length between the breaking C–O and forming C–C bonds.For PHBH, snapshots from GROMOS and AM1/GROMOS MD runs served as starting structures for AM1/GROMOS geometry optimisations. The resulting AM1/GROMOS transition structures were refined at the B3LYP/GROMOS level, by re-optimising the QM region and all surrounding residues within a distance of 5 Å. The B3LYP/GROMOS transition structures were then relaxed towards the associated reactants by careful stepwise energy minimizations, making sure that they are connected by a continuous path. The mapping coordinate used here was the difference in length between the breaking O–O and forming C–O bonds. Fig. S1 shows an optimized structure of the transition state within the active site, with a hydrogen bond between the transferring OH moiety and the backbone carbonyl of Pro 293.