A multistate empirical valence bond description of protonatable amino acids

C. Mark Maupin, Kim F. Wong, Alexander V. Soudackov, Sun Kim, Gregory A. Voth

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalJournal of Physical Chemistry A
Issue number2
StatePublished - Jan 19 2006
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry


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