title: A multistate empirical valence bond description of protonatable amino acids.
abstract: The multistate empirical valence bond (MS-EVB) model, which was developed for molecular dynamics simulations of proton transport in water and biomolecular systems, is extended for the modeling of protonatable amino acid residues in aqueous environments, specifically histidine and glutamic acid. The parameters of the MS-EVB force field are first determined to reproduce the geometries and energetics of the gas phase amino acid-water clusters. These parameters are then optimized to reproduce experimental pK(a) values. The free energy profiles for acid ionization and the corresponding pK(a) values are calculated by MS-EVB molecular dynamics simulations utilizing the umbrella sampling technique, with the center of excess charge coordinate chosen as the dissociation reaction coordinate. A general procedure for fitting the MS-EVB parameters is formulated, which allows for the parametrization of other amino acid residues with protonatable groups and the subsequent use of the MS-EVB approach for molecular dynamics simulations of proton transfer processes in proteins involving protonation/deprotonation of the protonatable amino acid groups.
authors.affiliation: Center for Biophysical Modeling and Simulation and Department of Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.
authors.forename: C Mark
authors.initials: CM
authors.lastname: Maupin
authors.forename: Kim F
authors.initials: KF
authors.lastname: Wong
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Soudackov
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004583:Electrons; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry; D011522:Protons
chemical_list: D000596:Amino Acids; D011506:Proteins; D011522:Protons