Doubly Polarized QM/MM with Machine Learning Chaperone Polarizability.
Doubly Polarized QM/MM with Machine Learning Chaperone Polarizability.
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DOI：
10.1021/acs.jctc.1c00567
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发表时间：
2021-12-14
影响因子：
5.5
通讯作者：
Pu, Jingzhi
中科院分区：
文献类型：
--
作者：
Kim, Bryant;Shao, Yihan;Pu, Jingzhi
半经验（SE）分子轨道方法的一个主要缺点是，与实验和从头算（AI）基准数据相比，它们严重低估了分子极化率。在溶液相反应的量子力学和分子力学相结合（QM/MM）的处理中，因此用SE方法描述的溶质往往对溶剂电场产生不充分的电子极化响应，这常常导致自由能曲线出现较大误差。为了解决这个问题，我们在此提出一种混合框架，通过高级分子极化率拟合来改善SE/MM方法的响应特性。具体而言，我们在量子力学（QM）原子上设置一组校正极化率（称为伴侣极化率），其大小通过机器学习（ML）确定，以重现沿最小自由能路径的凝聚相AI分子极化率。然后，这些伴侣极化率在类似于极化力场计算的机制中使用，以补偿常规SE/MM模拟中缺失的极化能。由于在此处理中QM原子既有SE波函数又有经典极化率，且都被分子力学（MM）电场极化，我们将这种方法命名为双极化QM/MM（dp - QM/MM）。我们在水中的 Menschutkin反应的自由能模拟中展示了这种新方法。以AM1/MM作为基础方法，我们表明，相对于密度泛函理论基准，机器学习伴侣将溶质分子极化率的误差从6.78 ų大幅降低至0.03 ų。伴侣校正导致产物区域产生约10 kcal/mol的额外极化能，使模拟的自由能曲线与实验结果更加吻合。此外，溶质 - 溶剂径向分布函数表明，当系统从电荷中性的反应物状态演变为电荷分离的过渡态和产物态时，伴侣极化率通过增强的溶剂化校正来改变自由能曲线。这些结果表明，由机器学习伴侣极化率实现的dp - QM/MM方法为基于SE/MM的自由能模拟中的极化不足问题提供了一种非常符合物理原理的解决方案。
A major shortcoming of semiempirical (SE) molecular orbital methods is their severe underestimation of molecular polarizability compared with experimental and ab initio (AI) benchmark data. In a combined quantum mechanical and molecular mechanical (QM/MM) treatment of solution-phase reactions, solute described by SE methods therefore tends to generate inadequate electronic polarization response to solvent electric fields, which often leads to large errors in free energy profiles. To address this problem, here we present a hybrid framework that improves the response property of SE/MM methods through high-level molecular-polarizability fitting. Specifically, we place on QM atoms a set of corrective polarizabilities (referred to as chaperone polarizabilities), whose magnitudes are determined from machine learning (ML) to reproduce the condensed-phase AI molecular polarizability along the minimum free energy path. These chaperone polarizabilities are then used in a machinery similar to a polarizable force field calculation to compensate for the missing polarization energy in the conventional SE/MM simulations. Because QM atoms in this treatment host SE wave functions as well as classical polarizabilities, both polarized by MM electric fields, we name this method doubly polarized QM/MM (dp-QM/MM). We demonstrate the new method on the free energy simulations of the Menshutkin reaction in water. Using AM1/MM as a base method, we show that ML chaperones greatly reduce the error in the solute molecular polarizability from 6.78 to 0.03 Å3 with respect to the density functional theory benchmark. The chaperone correction leads to ~10 kcal/mol of additional polarization energy in the product region, bringing the simulated free energy profiles to closer agreement with the experimental results. Furthermore, the solute-solvent radial distribution functions show that the chaperone polarizabilities modify the free energy profiles through enhanced solvation corrections when the system evolves from the charge-neutral reactant state to the charge-separated transition and product states. These results suggest that the dp-QM/MM method, enabled by ML chaperone polarizabilities, provides a very physical remedy for the underpolarization problem in SE/MM-based free energy simulations.
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影响因子：
8.6
作者：
Behler, Joerg;Parrinello, Michele
通讯作者：
Parrinello, Michele
影响因子：
3.7
作者：
Bartok, Albert P.;Kondor, Risi;Csanyi, Gabor
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Csanyi, Gabor
影响因子：
15
作者：
GAO, JL;XIA, XF
通讯作者：
XIA, XF
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4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD
影响因子：
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作者：
APPLEQUIST, J;CARL, JR;FUNG, KK
通讯作者：
FUNG, KK