Rackers Joshua A, Wang Qiantao, Liu Chengwen, Piquemal Jean-Philip, Ren Pengyu, Ponder Jay W
Program in Computational & Molecular Biophysics, Washington University, School of Medicine, Saint Louis, Missouri 63110, USA.
Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.
Phys Chem Chem Phys. 2016 Dec 21;19(1):276-291. doi: 10.1039/c6cp06017j.
The principal challenge of using classical physics to model biomolecular interactions is capturing the nature of short-range interactions that drive biological processes from nucleic acid base stacking to protein-ligand binding. In particular most classical force fields suffer from an error in their electrostatic models that arises from an ability to account for the overlap between charge distributions occurring when molecules get close to each other, known as charge penetration. In this work we present a simple, physically motivated model for including charge penetration in the AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) force field. With a function derived from the charge distribution of a hydrogen-like atom and a limited number of parameters, our charge penetration model dramatically improves the description of electrostatics at short range. On a database of 101 biomolecular dimers, the charge penetration model brings the error in the electrostatic interaction energy relative to the ab initio SAPT electrostatic interaction energy from 13.4 kcal mol to 1.3 kcal mol. The model is shown not only to be robust and transferable for the AMOEBA model, but also physically meaningful as it universally improves the description of the electrostatic potential around a given molecule.
运用经典物理学对生物分子相互作用进行建模的主要挑战在于捕捉驱动生物过程（从核酸碱基堆积到蛋白质-配体结合）的短程相互作用的本质。特别是，大多数经典力场在其静电模型中存在一个误差，该误差源于在分子彼此靠近时电荷分布重叠的情况下（即电荷渗透），无法准确考虑电荷分布的重叠。在这项工作中，我们提出了一个简单的、基于物理原理的模型，用于在AMOEBA（用于生物分子应用的原子多极优化能量学）力场中纳入电荷渗透。通过一个从类氢原子电荷分布导出的函数和有限数量的参数，我们的电荷渗透模型显著改善了对短程静电的描述。在一个包含101个生物分子二聚体的数据库上，电荷渗透模型将相对于从头算SAPT静电相互作用能的静电相互作用能误差从13.4千卡/摩尔降低到了1.3千卡/摩尔。该模型不仅对AMOEBA模型具有鲁棒性和可转移性，而且在物理上具有意义，因为它普遍改善了对给定分子周围静电势的描述。
