QM/MM free-energy perturbation compared to thermodynamic integration and umbrella sampling:: Application to an enzymatic reaction

被引：137

作者：

Kästner, J ^{[1
]}

Senn, HM ^{[1
]}

Thiel, S ^{[1
]}

Otte, N ^{[1
]}

Thiel, W ^{[1
]}

机构：

[1] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany

来源：

JOURNAL OF CHEMICAL THEORY AND COMPUTATION | 2006年 / 2卷 / 02期

关键词：

D O I：

10.1021/ct050252w

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

We used the free-energy perturbation (FEP) method in quantum mechanics/molecular mechanics (QM/MM) calculations to compute the free-energy profile of the hydroxylation reaction in the enzyme p-hydroxybenzoate hydroxylase (PHBH). k statistics were employed to analyze the FEP sampling including estimation of the sampling error. Various approximations of the free-energy perturbation method were tested. We find that it is adequate not only to freeze the density of the QM part during the dynamics at frozen QM geometry but also to approximate this density by electrostatic-potential-fitted point charges. It is advisable to include all atoms of a QM/MM link in the perturbation. The results of QM/MM-FEP for PHBH are in good agreement with those of thermodynamic integration and umbrella sampling.

引用

页码：452 / 461

页数：10

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