采用量子力学/分子力学自由能模拟对磷酰转移酶进行分析。
Analysis of Phosphoryl-Transfer Enzymes with QM/MM Free Energy Simulations.
作者信息
Roston Daniel, Lu Xiya, Fang Dong, Demapan Darren, Cui Qiang
机构信息
Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Madison, WI, United States.
Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Madison, WI, United States.
出版信息
Methods Enzymol. 2018;607:53-90. doi: 10.1016/bs.mie.2018.05.005. Epub 2018 Aug 14.
Abstract
We discuss the application of quantum mechanics/molecular mechanics (QM/MM) free energy simulations to the analysis of phosphoryl transfers catalyzed by two enzymes: alkaline phosphatase and myosin. We focus on the nature of the transition state and the issue of mechanochemical coupling, respectively, in the two enzymes. The results illustrate unique insights that emerged from the QM/MM simulations, especially concerning the interpretation of experimental data regarding the nature of enzymatic transition states and coupling between global structural transition and catalysis in the active site. We also highlight a number of technical issues worthy of attention when applying QM/MM free energy simulations, and comment on a number of technical and mechanistic issues that require further studies.
摘要
我们讨论了量子力学/分子力学（QM/MM）自由能模拟在分析两种酶（碱性磷酸酶和肌球蛋白）催化的磷酰基转移反应中的应用。我们分别关注了这两种酶中过渡态的性质和机械化学偶联问题。结果表明，QM/MM模拟产生了独特的见解，特别是在解释有关酶促过渡态性质以及活性位点中全局结构转变与催化之间偶联的实验数据方面。我们还强调了应用QM/MM自由能模拟时一些值得关注的技术问题，并对一些需要进一步研究的技术和机理问题进行了评论。
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