Development of a multipoint model for sulfur in proteins: A new parametrization scheme to reproduce high‐levelab initiointeraction energies

Abstract

To properly represent weak hydrogen bonds to sulfur in biological systems, a new multipoint model of atomic sulfur for the amino acid methionine is introduced. This is of particular importance for the description of ligand-protein interactions. The parametrization is performed by fitting the nonbonding parameters of dimethyl sulfide to high level ab initio interaction energy surfaces of the dimethyl sulfide-methanol system and incorporating them in the GROMACS force field. Two examples demonstrate the performance of the new model, the molecular dynamics simulations of the hRAR receptor and of alpha-lytic protease. In hRAR the origin of the discrimination between the R- and S-enantiomers of the synthetic ligand BMS 184394 is explained, and in the simulation of the alpha-lytic protease it is shown that no artificial long range disorders are introduced by the new parametrization.