A Comparison of QM/MM Simulations with and without the Drude Oscillator Model Based on Hydration Free Energies of Simple Solutes.
A Comparison of QM/MM Simulations with and without the Drude Oscillator Model Based on Hydration Free Energies of Simple Solutes.
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DOI：
10.3390/molecules23102695
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发表时间：
2018-10-19
期刊：
影响因子：
--
通讯作者：
York DM
中科院分区：
文献类型：
--
作者：
König G;Pickard FC;Huang J;Thiel W;MacKerell AD;Brooks BR;York DM
在分子模拟中，保持特定分子间相互作用和非特定溶剂相互作用之间的适当平衡是至关重要的，特别是在预测凝聚相的结合亲和力或反应速率时。表征溶剂亲和力的最严格的度量是溶剂化自由能，它对应于从气相到溶液的转移。由于在此过程中静电环境的剧烈变化，对模型中的极化响应也是一个严格的考验。本文采用CHARMM固定电荷场和极化力场预测了12种简单溶质的水化自由能。然后利用MP2、Hartree-Fock、密度泛函方法（BLYP、B3LYP、M06-2X）和半经验方法（OM2和AM1）对得到的经典系综进行重新加权，得到QM/MM水化自由能。我们的模拟测试了量子力学方法与分子力学水模型和溶质伦纳德-琼斯参数的兼容性。在所有情况下，得到的QM/MM水化自由能都不如纯经典结果，QM/MM德鲁德力场预测仅略好于QM/MM固定电荷结果。此外，不同量子方法的QM/MM结果差异很大，极化和固定电荷水模型的趋势几乎是相反的。虽然这并不一定意味着质量管理模型本身存在缺陷，但它强调了开发一致且平衡的质量管理/质量管理交互的需要。QM/MM模拟的QM和MM组件必须匹配，以避免由于偏颇的溶质-溶剂相互作用而产生的伪影。最后，我们讨论了利用分子力学力场自动适应目标量子方法来提高多尺度自由能模拟的收敛性和效率的策略。
Maintaining a proper balance between specific intermolecular interactions and non-specific solvent interactions is of critical importance in molecular simulations, especially when predicting binding affinities or reaction rates in the condensed phase. The most rigorous metric for characterizing solvent affinity are solvation free energies, which correspond to a transfer from the gas phase into solution. Due to the drastic change of the electrostatic environment during this process, it is also a stringent test of polarization response in the model. Here, we employ both the CHARMM fixed charge and polarizable force fields to predict hydration free energies of twelve simple solutes. The resulting classical ensembles are then reweighted to obtain QM/MM hydration free energies using a variety of QM methods, including MP2, Hartree–Fock, density functional methods (BLYP, B3LYP, M06-2X) and semi-empirical methods (OM2 and AM1 ). Our simulations test the compatibility of quantum-mechanical methods with molecular-mechanical water models and solute Lennard–Jones parameters. In all cases, the resulting QM/MM hydration free energies were inferior to purely classical results, with the QM/MM Drude force field predictions being only marginally better than the QM/MM fixed charge results. In addition, the QM/MM results for different quantum methods are highly divergent, with almost inverted trends for polarizable and fixed charge water models. While this does not necessarily imply deficiencies in the QM models themselves, it underscores the need to develop consistent and balanced QM/MM interactions. Both the QM and the MM component of a QM/MM simulation have to match, in order to avoid artifacts due to biased solute–solvent interactions. Finally, we discuss strategies to improve the convergence and efficiency of multi-scale free energy simulations by automatically adapting the molecular-mechanics force field to the target quantum method.
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
影响因子：
4.4
作者：
BENNAIM, A;MARCUS, Y
通讯作者：
MARCUS, Y
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD
影响因子：
3.3
作者：
Chang, Jaeeon;Lenhoff, Abraham M.;Sandler, Stanley I.
通讯作者：
Sandler, Stanley I.