Department of Chemistry, M.V. Lomonosov Moscow State University, 1/3 Leninskie Gory, Moscow 119991, Russian Federation.
Chem Biol Interact. 2013 Mar 25;203(1):51-6. doi: 10.1016/j.cbi.2012.08.027. Epub 2012 Sep 13.
We re-visited the results of quantum mechanics--molecular mechanics (QM/MM) approaches aiming to construct the reaction energy profile for the acylation stage of acetylcholine hydrolysis by acetylcholinesterase. The main emphasis of this study was on the energy of the first tetrahedral intermediate (TI) relative to the level of the enzyme-substrate (ES) complex for which contradictory data from different works had been reported. A new series of stationary points on the potential energy surface was calculated by using electronically embedding QM/MM schemes when starting from the crystal structure mimicking features of the reaction intermediate (PDB ID: 2VJA). A thoughtful analysis allows us to conclude that the energy of TI should be lower than that of ES, and a proper treatment of contributions from the oxyanion hole residues accounts for their relative positions.
我们重新审视了量子力学-分子力学（QM/MM）方法的结果，这些方法旨在构建乙酰胆碱水解酶催化酰化阶段的反应能量曲线。本研究的主要重点是第一个四面体型中间体（TI）相对于酶-底物（ES）复合物的能量，因为不同研究报告的数据存在矛盾。通过使用电子嵌入 QM/MM 方案，从模拟反应中间体特征的晶体结构（PDB ID：2VJA）出发，计算了新的势能面上的一系列稳定点。通过深入分析，我们可以得出结论，TI 的能量应该低于 ES 的能量，并且适当考虑氧阴离子穴残基的贡献可以解释它们的相对位置。
