Quantum mechanical/molecular mechanical analysis of mechanisms of enzyme action. Human acetylcholinesterase

被引：0
|
作者：
S. V. Lushchekina
I. A. Kaliman
B. L. Grigorenko
A. V. Nemukhin
S. D. Varfolomeev
机构：
[1] Russian Academy of Sciences,N. M. Emanuel’ Institute of Biochemical Physics
[2] M. V. Lomonosov Moscow State University,Department of Chemistry
来源：
Russian Chemical Bulletin | 2011年 / 60卷
关键词：
acetylcholinesterase; reaction mechanism; acetylcholine; QM/MM method; quantum subsystem; density functional theory (DFT); BB1K and B3LYP functionals; AMBER force field;
D O I：
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学科分类号：
摘要：
The influence of the system separation into the QM and MM parts on the result of quantum mechanical/molecular mechanical (QM/MM) modeling of acetylcholine hydrolysis in the acetylcholinesterase active site was considered. The minimum acceptable quantum subsystem that provides an adequate description of the enzymatic reaction energy profile was identified. The computed energy profiles were analyzed and possible inaccuracies in QM/MM calculations were estimated. The fairly high tetrahedral intermediate stability was demonstrated, which is in a good agreement with the newest experimental observations.
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页码：2196 / 2204
页数：8
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