A Toolkit to Fit Nonbonded Parameters from and for Condensed Phase Simulations.

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.