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

采用基于混合哈密顿模型（QM/MM）的微扰理论计算自由能，结合溶剂构型的蒙特卡罗采样，得到了溶剂化自由能的变化。我们设计了一种特殊的程序来分析二维自由能表面，以获得对两种体系之间反应机理差异的独特见解。以100个H_2O分子为溶剂模型，计算了烷基氯/氯交换/转化反应的二维自由能面。将水团簇的NVT系综划分为构型子集，每个子集对应不同拓扑的氢键模式，并计算了氢键模式的相对摩尔亥姆霍兹能。该方法是基于标准蒙特卡罗技术与定义的氢键模式的结合。我们推导并实现了用于生化应用的分子动力学方法。该实现允许表征实际酶的功能，考虑到它们的热运动。

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.