Laboratoire de Pharmacochimie Moléculaire et Cellulaire, U648 INSERM, UFR Biomédicale, Université Paris Descartes, 45, rue des Saints-Pères, 75006 Paris, France UPMC Univ Paris 06, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France, and CNRS, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France.
J Chem Theory Comput. 2008 Oct 14;4(10):1659-68. doi: 10.1021/ct800200j.
We analyze the intermolecular interaction energies stabilizing the complex of ethanol in the binding site of alcohol dehydrogenase Zn-metalloenzyme (ADH). In this site Zn(II) is ligated by two cysteine and one imidazole residue and by the ethanol substrate. Ethanol is stacked over a phenylalanine residue. The system has been studied by means of SIBFA (Sum of Interactions Between Fragments Ab initio computed) polarizable molecular mechanics (PMM) supplemented by quantum chemical (QC) computations at various levels of theory. The nonadditivities of the QC interaction energies can be traced back by energy-decomposition analyses and are essentially due to polarization, charge-transfer, and electron correlation energies. These contributions can be reproduced by PMM computations. Interestingly, the polarization energy associated with the presence of the benzene ring in the ADH complex is canceled due to many-body/nonadditivity effects. Therefore this ring does not contribute to stabilization prior to including electron correlation/dispersion effects in the QC calculations or in the absence of the PMM dispersion energy contribution. When these effects are taken into account, the stabilization it contributes is in the 3-9 kcal/mol range, reflecting the need for an accurate reproduction of all components of the interaction energy by PMM.
我们分析了稳定乙醇与醇脱氢酶 Zn 金属酶（ADH）结合部位复合物的分子间相互作用能。在该部位，Zn(II) 由两个半胱氨酸和一个咪唑残基以及乙醇底物配位。乙醇堆积在苯丙氨酸残基上。该系统通过 SIBFA（片段间相互作用总和从头算计算）极化分子力学（PMM）进行了研究，并辅以各种理论水平的量子化学（QC）计算。QC 相互作用能的不可加性可以通过能量分解分析来追踪，主要归因于极化、电荷转移和电子相关能。这些贡献可以通过 PMM 计算来再现。有趣的是，由于多体/不可加性效应，ADH 复合物中苯环的极化能被抵消。因此，在包括 QC 计算中的电子相关/色散效应或不包括 PMM 色散能贡献之前，该环对稳定化没有贡献。当考虑这些效应时，它所贡献的稳定化能在 3-9 kcal/mol 范围内，反映了 PMM 准确再现相互作用能所有组成部分的必要性。
