Molecular Dynamics with Conformationally Dependent, Distributed Charges

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.