Molecular Dynamics with Conformationally Dependent, Distributed Charges

TL;DR

This paper introduces a flexible minimal distributed charge model (fMDCM) that dynamically relocates charges based on molecular geometry, significantly improving electrostatic potential accuracy and stability in molecular dynamics simulations.

Contribution

The paper presents a novel, geometry-dependent charge relocation method (fMDCM) that enhances electrostatic modeling in molecular simulations compared to traditional fixed charge models.

Findings

fMDCM achieves 0.5 kcal/mol ESP accuracy on small molecules.

MD simulations with fMDCM show stable energy fluctuations at 300 K over 10 ns.

fMDCM outperforms MDCM and point charges in electrostatic accuracy.

Abstract

Accounting for geometry-induced changes in the electronic distribution in molecular simulation is important for capturing effects such as charge flow, charge anisotropy and polarization. Multipolar force fields have demonstrated their ability to qualitatively and correctly represent chemically significant features such as sigma holes. It has also been shown that off-center point charges offer a compact alternative with similar accuracy. Here it is demonstrated that allowing relocation of charges within a minimally distributed charge model (MDCM) with respect to their reference atoms is a viable route to capture changes in the molecular charge distribution depending on geometry. The approach, referred to as ``flexible MDCM'' (fMDCM) is validated on a number of small molecules and provides accuracies in the electrostatic potential (ESP) of 0.5 kcal/mol on average compared with reference data from electronic structure calculations whereas MDCM and point charges have root mean squared errors of a factor of 2 to 5 higher. In addition, MD simulations in the $NVE$ ensemble using fMDCM for a box of flexible water molecules with periodic boundary conditions show a width of 0.1 kcal/mol for the fluctuation around the mean at 300 K on the 10 ns time scale. The accuracy in capturing the geometry dependence of the ESP together with the long-time stability in energy conserving simulations makes fMDCM a promising tool to introduce advanced electrostatics into atomistic simulations.