Alchemical Hydration Free-Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Polarization Approach.,Journal of Chemical Theory and Computation

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Alchemical Hydration Free-Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Polarization Approach.
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2020-01-23 , DOI: 10.1021/acs.jctc.9b01139
Braden D Kelly ₁ , William R Smith _{1,

2,

3}

Affiliation

We present a methodology using fixed charge force fields for alchemical solvation free energy calculations which accounts for the change in polarity that the solute experiences as it transfers from the gas-phase to the condensed phase. We update partial charges using QM/MM snapshots, decoupling the electric field appropriately when updating the partial charges. We also show how to account for the cost of self-polarization. We test our methodology on 30 molecules ranging from small polar to large druglike molecules. We use Minimum Basis Iterative Stockholder (MBIS), Restrained Electrostatic Potential (RESP), and AM1-BCC partial charge methodologies. Using our method with MP2/cc-pVTZ and MBIS partial charges yields an average absolute deviation (AAD) of 6.3 kJ·mol-1 in comparison with the AM1-BCC result of 8.6 kJ·mol-1. AM1-BCC is within experimental uncertainty on 10% of the data compared to 30% with our method. We conjecture that results can be further improved by using Lennard-Jones and torsional parameters refitted to MBIS and RESP partial charge methods that use high levels of theory.

中文翻译：

使用分子动力学的显式极化和诱导的极性去耦进行炼金水合自由能的计算：动态极化方法。

我们提出了一种使用固定电荷力场进行炼金法溶剂化自由能计算的方法，该方法说明了溶质从气相转移到冷凝相时所经历的极性变化。我们使用QM / MM快照更新部分电荷，在更新部分电荷时适当地将电场解耦。我们还展示了如何考虑自极化的成本。我们对30种分子（从小极性分子到大分子药物分子）进行了测试。我们使用最小基本迭代股东（MBIS），约束静电势（RESP）和AM1-BCC部分充电方法。与MP1 / cc-pVTZ和MBIS部分电荷一起使用我们的方法，与AM1-BCC的结果8.6 kJ·mol-1相比，平均绝对偏差（AAD）为6.3 kJ·mol-1。AM1-BCC在10％的数据的实验不确定性范围内，而我们的方法为30％。我们推测，通过使用Lennard-Jones以及使用高水平理论的MBIS和RESP局部充电方法改正的扭转参数，可以进一步改善结果。

更新日期：2020-01-24

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