CHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses.

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TitleCHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses.
Publication TypeJournal Article
Year of Publication2009
AuthorsGuvench, O, Hatcher, ER, Venable, RM, Pastor, RW, Mackerell, AD
JournalJ Chem Theory Comput
Volume5
Issue9
Pagination2353-2370
Date Published2009 Aug 20
ISSN1549-9626
Abstract

We present an extension of the CHARMM hexopyranose monosaccharide additive all-atom force field to enable modeling of glycosidic-linked hexopyranose polysaccharides. The new force field parameters encompass 1→1, 1→2, 1→3, 1→4, and 1→6 hexopyranose glycosidic linkages, as well as O-methylation at the C(1) anomeric carbon, and are developed to be consistent with the CHARMM all-atom biomolecular force fields for proteins, nucleic acids, and lipids. The parameters are developed in a hierarchical fashion using model compounds containing the key atoms in the full carbohydrates, in particular O-methyl-tetrahydropyran and glycosidic-linked dimers consisting of two molecules of tetrahyropyran or one of tetrahydropyran and one of cyclohexane. Target data for parameter optimization include full two-dimensional energy surfaces defined by the Φ/Ψ glycosidic dihedral angles in the disaccharide analogs as determined by quantum mechanical MP2/cc-pVTZ single point energies on MP2/6-31G(d) optimized structures (MP2/cc-pVTZ//MP2/6-31G(d)). In order to achieve balanced, transferable dihedral parameters for the Φ/Ψ glycosidic dihedral angles, surfaces for all possible chiralities at the ring carbon atoms involved in the glycosidic linkages are considered, resulting in over 5000 MP2/cc-pVTZ//MP2/6-31G(d) conformational energies. Also included as target data are vibrational frequencies, pair interaction energies and distances with water molecules, and intramolecular geometries including distortion of the glycosidic valence angle as a function of the glycosidic dihedral angles. The model-compound optimized force field parameters are validated on full disaccharides through comparison of molecular dynamics results to available experimental data. Good agreement is achieved with experiment for a variety of properties including crystal cell parameters and intramolecular geometries, aqueous densities, and aqueous NMR coupling constants associated with the glycosidic linkage. The newly-developed parameters allow for the modeling of linear, branched, and cyclic hexopyranose glycosides both alone and in heterogenous systems including proteins, nucleic acids and/or lipids when combined with existing CHARMM biomolecular force fields.

DOI10.1021/ct900242e
Alternate JournalJ Chem Theory Comput
PubMed ID20161005
PubMed Central IDPMC2757763
Grant ListF32 CA119771 / CA / NCI NIH HHS / United States
R01 GM070855 / GM / NIGMS NIH HHS / United States
R01 GM070855-04 / GM / NIGMS NIH HHS / United States