Polarizable empirical force field for sulfur-containing compounds based on the classical Drude oscillator model.

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TitlePolarizable empirical force field for sulfur-containing compounds based on the classical Drude oscillator model.
Publication TypeJournal Article
Year of Publication2010
AuthorsZhu, X, Mackerell, AD
JournalJ Comput Chem
Volume31
Issue12
Pagination2330-41
Date Published2010 Sep
ISSN1096-987X
KeywordsAmino Acids, Amino Acids, Sulfur, Crystallography, X-Ray, Databases, Factual, Electrochemistry, Electromagnetic Fields, Energy Transfer, Models, Chemical, Models, Molecular, Molecular Conformation, Proteins, Quantum Theory, Solubility, Solvents, Sulfhydryl Compounds, Sulfides, Sulfur Compounds, Water
Abstract

Condensed-phase computational studies of molecules using molecular mechanics approaches require the use of force fields to describe the energetics of the systems as a function of structure. The advantage of polarizable force fields over nonpolarizable (or additive) models lies in their ability to vary their electronic distribution as a function of the environment. Toward development of a polarizable force field for biological molecules, parameters for a series of sulfur-containing molecules are presented. Parameter optimization was performed to reproduce quantum mechanical and experimental data for gas phase properties including geometries, conformational energies, vibrational spectra, and dipole moments as well as for condensed phase properties such as heats of vaporization, molecular volumes, and free energies of hydration. Compounds in the training set include methanethiol, ethanethiol, propanethiol, ethyl methyl sulfide, and dimethyl disulfide. The molecular volumes and heats of vaporization are in good accordance with experimental values, with the polarizable model performing better than the CHARMM22 nonpolarizable force field. Improvements with the polarizable model were also obtained for molecular dipole moments and in the treatment of intermolecular interactions as a function of orientation, in part due to the presence of lone pairs and anisotropic atomic polarizability on the sulfur atoms. Significant advantage of the polarizable model was reflected in calculation of the dielectric constants, a property that CHARMM22 systematically underestimates. The ability of this polarizable model to accurately describe a range of gas and condensed phase properties paves the way for more accurate simulation studies of sulfur-containing molecules including cysteine and methionine residues in proteins.

DOI10.1002/jcc.21527
Alternate JournalJ Comput Chem
PubMed ID20575015
PubMed Central IDPMC2923574
Grant ListR01 GM072558 / GM / NIGMS NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States
R01 GM051501-13 / GM / NIGMS NIH HHS / United States
R01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States
R01 GM072558-08 / GM / NIGMS NIH HHS / United States
GM072558 / GM / NIGMS NIH HHS / United States