Accurate and Efficient Treatment of Continuous Solute Charge Density in the Mean-Field QM/MM Free Energy Calculation
Accurate and Efficient Treatment of Continuous Solute Charge Density in the Mean-Field QM/MM Free Energy Calculation
复制标题
平均场 QM/MM 自由能计算中连续溶质电荷密度的准确高效处理
DOI：
10.1021/ct300831t
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发表时间：
2013
影响因子：
5.5
通讯作者：
T. Yamamoto
中科院分区：
文献类型：
--
作者：
H. Nakano;T. Yamamoto
QM/MM自由能计算是计算要求，因为需要大量的电子结构计算。一个实际的方法，以减少计算成本是基于平均场近似，计算QM波函数的存在下，部分或全部平均的潜在的MM环境。为了获得后者的潜力，它是常见的，首先表示的QM分子的点电荷，然后进行MM分子的统计抽样。然而，点电荷近似的缺点是，它往往高估静电（ES）在短程的相互作用，这可能会引起发散问题的自洽迭代。因此，在本文中，我们考虑基于连续QM电荷密度的平均场QM/MM方法的更准确和鲁棒的实现，这里利用以下组合：（i）对QM分子产生的ES电势进行基于网格的处理，这允许在QM电荷密度存在的情况下对MM分子进行有效采样，以及（ii）QM/MM-Ewald方法在平均场框架下的适应性，以消除长程ES相互作用中的截止误差。作为一个数值试验，我们将所得到的方法应用于水溶液中的几个基准反应，并表明基于密度的方法基本上消除了发散问题，同时提供与实验一致的自由能分布。此外，我们测试的效用最近提出的屏蔽电荷模型的QM电荷密度，并表明后者也表现良好的自由能计算。这些结果表明，明确包括电荷穿透效应是有益的，以提高平均场QM/MM计算的准确性和稳定性。
QM/MM free energy calculation is computationally demanding because of the need for an excessive number of electronic structure calculations. A practical approach for reducing the computational cost is that based on mean field approximation, which calculates the QM wave function in the presence of a partially or totally averaged potential of the MM environment. For obtaining the latter potential, it is common to first represent the QM molecule in terms of point charges and then perform statistical sampling of MM molecules. However, the point charge approximation has the drawback that it tends to overestimate electrostatic (ES) interactions at short-range, which may give rise to a divergence problem in the self-consistent iterations. In this paper, we thus consider a more accurate and robust implementation of mean-field QM/MM method based on continuous QM charge density, here utilizing the following combination: (i) grid-based treatment of ES potential generated by the QM molecule, which allows for an efficient sampling of MM molecules in the presence of QM charge density, and (ii) adaptation of the QM/MM-Ewald method to the mean-field framework for eliminating cutoff errors in the long-range ES interactions. As a numerical test, we apply the obtained method to several benchmark reactions in aqueous solution, and show that the density-based method essentially eliminates the divergence problem while providing the free energy profile consistent with experiment. In addition, we test the utility of a recently proposed screened charge model for the QM charge density and show that the latter also performs well for the free energy calculation. These results suggest that explicit inclusion of charge penetration effects is beneficial for improving the accuracy and stability of the mean-field QM/MM calculation.