title: Development of a multipoint model for sulfur in proteins: a new parametrization scheme to reproduce high-level ab initio interaction 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.
authors.affiliation: Ruhr-Universität Bochum, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Wennmohs
authors.forename: M
authors.initials: M
authors.lastname: Schindler
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D018168:Receptors, Retinoic Acid / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry; D012984:Software; D013237:Stereoisomerism; D013455:Sulfur / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: C500038:BMS 184394; D008024:Ligands; D009281:Naphthalenes; D011506:Proteins; D018168:Receptors, Retinoic Acid; D013455:Sulfur; D012697:Serine Endopeptidases; C021826:myxobacter alpha-lytic proteinase