Hédin Florent, El Hage Krystel, Meuwly Markus
Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Department of Chemistry, Brown University , Providence, Rhode Island 02912, United States.
J Chem Inf Model. 2016 Aug 22;56(8):1479-89. doi: 10.1021/acs.jcim.6b00280. Epub 2016 Aug 5.
The quality of atomistic simulations depends decisively on the accuracy of the underlying energy function (force field). Of particular importance for condensed-phase properties are nonbonded interactions, including the electrostatic and Lennard-Jones terms. Permanent atomic multipoles (MTPs) are an extension to common point-charge (PC) representations in atomistic simulations. MTPs are commonly determined from and fitted to an ab initio Electrostatic Potential (ESP), and Lennard-Jones (LJ) parameters are obtained from comparison of experimental and computed observables using molecular dynamics (MD) simulations. For this a set of thermodynamic observables such as density, heat of vaporization, and hydration free energy is chosen, to which the parametrization is fitted. The current work introduces a comprehensive computing environment (Fitting Wizard (FW)) for optimizing nonbonded interactions for atomistic force fields of different qualities. The FW supports fitting of standard PC-based force fields and more physically motivated multipolar (MTP) force fields. A broader study including 20 molecules ranging from N-methyl-acetamide and benzene to halogenated benzenes, phenols, anilines, and pyridines yields a root mean squared deviation for hydration free energies of 0.36 kcal/mol over a range of 8 kcal/mol. It is furthermore shown that PC-based force fields are not necessarily inferior compared to MTP parametrizations depending on the molecule considered.
原子模拟的质量决定性地取决于基础能量函数（力场）的准确性。对于凝聚相性质而言，非键相互作用尤为重要，其中包括静电项和 Lennard-Jones 项。永久原子多极矩（MTPs）是原子模拟中对常见点电荷（PC）表示的一种扩展。MTPs 通常由从头算静电势（ESP）确定并拟合得到，而 Lennard-Jones（LJ）参数则通过使用分子动力学（MD）模拟比较实验和计算得到的可观测量来获得。为此，选择了一组热力学可观测量，如密度、汽化热和水合自由能，并对参数化进行拟合。当前工作引入了一个综合计算环境（拟合向导（FW）），用于优化不同质量的原子力场的非键相互作用。FW 支持对基于标准 PC 的力场和更具物理动机的多极（MTP）力场进行拟合。一项更广泛的研究涵盖了从 N-甲基乙酰胺、苯到卤代苯、苯酚、苯胺和吡啶等 20 种分子，在 8 kcal/mol 的范围内，水合自由能的均方根偏差为 0.36 kcal/mol。此外还表明，根据所考虑的分子，基于 PC 的力场不一定比 MTP 参数化差。
