QM/MM-MC and QM/MM-MD simulations for reactions in solution

自由能计算微扰理论的基础上的混合哈密顿模型（QM/MM）结合Monte Carlo抽样的溶剂配置的自由能的变化被用来获得溶剂化自由能。我们设计了一个特殊的程序来分析二维自由能表面，以获得独特的洞察两个系统之间的反应机制的差异。以100个水分子为溶剂模型，计算了烷基氯/氯离子交换/转化反应的二维自由能面，将水分子团簇的NVT系综划分为对应于不同拓扑氢键模式的构型子集，并计算了氢键模式的相对摩尔Helmholtz能.该方法是基于标准的Monte Carlo技术与定义的氢键模式相结合，我们推导并实现了ONIOM-分子动力学方法的生物化学应用。该实施方式允许表征考虑到它们的热运动的真实的酶的功能。

The free-energy calculation by perturbation theory based on a mixed-Hamiltonian model (QM/MM) combined with Monte Carlo sampling of the solvent configurations was used to obtain the changes in solvation free energy. We devised a special procedure to analyze the two-dimensional free-energy surfaces to gain unique insight into the differences in the reaction mechanisms between the two systems. Two-dimensional free-energy surfaces are calculated for alkyl chloride/chloride exchange/inversion reactions surrounded by one hundred H_2O molecules as a model of solvent.The NVT ensemble of water cluster is divided into the configurational subsets, which correspond to the topology-distinct H-bond patterns, and the relative molar Helmholtz energies of the H-bond patterns are evaluated. The method is based on the combination of standard Monte Carlo techniques with defined H-bond patterns.We derived and implemented the ONIOM-molecular dynamics method for biochemical applications. The implementation allows the characterization of the functions of the real enzymes taking account of their thermal motion.