On combining Thole's induced point dipole model with fixed charge distributions in molecular mechanics force fields.

Abstract

The Thole induced point dipole model is combined with three different point charge fitting methods, Merz-Kollman (MK), charges from electrostatic potentials using a grid (CHELPG), and restrained electrostatic potential (RESP), and two multipole algorithms, distributed multipole analysis (DMA) and Gaussian multipole model (GMM), which can be used to describe the electrostatic potential (ESP) around molecules in molecular mechanics force fields. This is done to study how the different methods perform when intramolecular polarizability contributions are self-consistently removed from the fitting done in the force field parametrization. It is demonstrated that the polarizable versions of the partial charge models provide a good compromise between accuracy and computational efficiency in describing the ESP of small organic molecules undergoing conformational changes. For the point charge models, the inclusion of polarizability reduced the the average root mean square error of ESP over the test set by 4-10%.