Calculations of Solvation Free Energy through Energy Reweighting from Molecular Mechanics to Quantum Mechanics
Calculations of Solvation Free Energy through Energy Reweighting from Molecular Mechanics to Quantum Mechanics
复制标题
通过从分子力学到量子力学的能量重加权计算溶剂化自由能
DOI：
10.1021/acs.jctc.5b00920
复制
发表时间：
2016-02-01
影响因子：
5.5
通讯作者：
Mei, Ye
中科院分区：
文献类型：
--
作者：
Jia, Xiangyu;Wang, Meiting;Mei, Ye
在这项工作中，计算了第四次蛋白质和配体建模统计评估 (SAMPL4) 中 20 个有机分子的溶剂化自由能。相空间采样在分子力学水平上进行，并使用贝内特接受比 (BAR) 估计相关的自由能变化。然后通过间接非玻尔兹曼贝内特接受比（NBB）或热力学微扰（TP）方法计算量子力学（QM）校正。我们表明，BAR+TP 给出了高斯极限下计算的溶剂化自由能的最小解析方差，并且在实践中表现略好于 NBB。此外，TP中QM计算的费用仅为NBB中的一半。我们还表明，将偏置势定义为溶质溶剂相互作用能的差值，而不是总能量，可以更快地收敛计算的溶剂化自由能，但可能收敛到不同的值。基于之前发表的实验溶剂化自由能，本研究发现BLYP比MP2和其他一些后来的泛函如B3LYP、M06-2X和omega B97X-D产生更好的结果。
In this work, the solvation free energies of 20 organic molecules from the 4th Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL4) have been calculated. The sampling of phase space is carried out at a molecular mechanical level, and the associated free energy changes are estimated using the Bennett Acceptance:Ratio (BAR). Then the quantum mechanical (QM) corrections are computed through the indirect Non-Boltzmann Bennett's acceptance ratio (NBB) or the thermodynamics perturbation (TP) method. We show that BAR+TP gives a minimum analytic variance for the calculated solvation free energy at the Gaussian limit and performs slightly better than NBB in practice. Furthermore, the expense of the QM calculations in TP is only half of that in NBB, We also show that defining the biasing potential as the difference of the solute solvent interaction energy, instead of the total energy, can converge the calculated solvation free energies much faster but possibly to different values. Based on the experimental solvation free energies which have been published before, it is discovered in this study that BLYP yields better results than MP2 and some other later functionals such as B3LYP, M06-2X, and omega B97X-D.