TIP5P-Consistent Treatment of Electrostatics for Biomolecular Simulations.

Abstract

The inclusion of zero-mass point charges around electronegative atoms, such as oxygen, within molecular mechanical force fields is known to improve hydrogen-bonding directionality. In parallel, inclusion of lone-pairs (LPs) in the TIP5P water model increased its ability to reproduce both gas-phase and condensed-phase properties over its non-LP predecessor, TIP3P. Currently, most biomolecular parameter sets compute partial atomic charges via fitting of the classical molecular electrostatic potential (MEP) to the quantum mechanical MEP. Application of this methodology to optimize lone-pair description is therefore consistent with the current approach to modeling electrostatics and is straightforward to implement. Here, we present an atom-type specific lone-pair model, which leads to the most optimal LP placement for each atom type, and, notably, results in reproduction of the lone-pair description present in TIP5P. Carbohydrates are rich in hydroxyl groups, and development of a lone-pair inclusive carbohydrate force field for use with a lone-pair containing water model, such as TIP5P, ensures the compatibility between these two models. Implementation of this lone-pair model improves the geometry and energetics for a series of hydrogen-bonded clusters and the properties of several small molecule crystals over the non-LP containing force field.