Energy Analysis of Zn Polycoordination in a Metalloprotein Environment and of the Role of a Neighboring Aromatic Residue. What Is the Impact of Polarization?
Energy Analysis of Zn Polycoordination in a Metalloprotein Environment and of the Role of a Neighboring Aromatic Residue. What Is the Impact of Polarization?
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DOI：
10.1021/ct800200j
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Gresh, Nohad
中科院分区：
文献类型：
--
作者：
de Courcy, Benoit;Piquemal, Jean-Philip;Gresh, Nohad
本文分析了乙醇脱氢酶锌金属酶（ADH）结合位点稳定乙醇络合物的分子间相互作用能。在这个位点上，锌（II）由两个半胱氨酸和一个咪唑残基以及乙醇底物连接。乙醇堆积在苯丙氨酸残渣上。利用SIBFA（从头计算的碎片间相互作用和）极化分子力学（PMM）和量子化学（QC）在不同理论水平上的计算对该体系进行了研究。QC相互作用能量的非可加性可以通过能量分解分析追溯到，主要是由于极化、电荷转移和电子相关能。这些贡献可以通过PMM计算再现。有趣的是，由于多体/非加性效应，与ADH配合物中苯环存在相关的极化能被抵消。因此，在QC计算中包括电子相关/色散效应之前，或者在没有PMM色散能量贡献的情况下，该环对稳定没有贡献。当考虑到这些影响时，它所贡献的稳定在3-9千卡/摩尔范围内，反映了PMM需要精确再现相互作用能的所有组成部分。
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.