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

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.

Loop Motions Important to Product Expulsion in the Thermobifida fusca Glycoside Hydrolase Family 6 Cellobiohydrolase from Structural and Computational Studies

“…The CHARMM22 force field parameters (47,48) with the CMAP correction (49 -51) were used for the enzyme, and the C35 carbohydrate force field parameters (52,53) were used for the substrates. Ions were added into the systems to maintain charge neutrality.…”

Evolution of Xylan Substitution Patterns in Gymnosperms and Angiosperms: Implications for Xylan Interaction with Cellulose

“…11). This pattern is representative of a conifer xylan, and the substitutions were added according to the CHARMM36 force field internal coordinates (Guvench et al, 2009;Raman et al, 2010). Subsequently, the cellulose fibril was cut in the middle, parallel to the plane (110), so as to consider only the chains close to the face where the xylan is adsorbed (Fig.…”

Bilayer Properties of Lipid A from Various Gram-Negative Bacteria

“…The force-field parameters for each lipid A were assigned from the CHARMM36 force field for LPS (42), lipids (43), carbohydrates (44)(45)(46), and proteins (47). Each system contains 72 lipid A molecules (36 in each leaflet) with neutralizing Ca 2þ ions in 150 mM KCl.…”