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

Area of Science:

• Computational Chemistry
• Biomolecular Modeling
• Carbohydrate Chemistry

Background:

• CHARMM force fields are essential for molecular dynamics simulations of biomolecules.
• Accurate modeling of complex carbohydrates, like polysaccharides, requires specialized force field parameters.

Purpose of the Study:

• To extend the CHARMM all-atom force field for hexopyranose monosaccharides to model glycosidic-linked hexopyranose polysaccharides.
• To develop and validate new force field parameters for various hexopyranose glycosidic linkages and O-methylation.

Main Methods:

• Hierarchical parameter development using model compounds (O-methyl-tetrahydropyran, glycosidic-linked dimers).
• Quantum mechanical calculations (MP2/cc-pVTZ//MP2/6-31G(d)) for energy surfaces of glycosidic dihedral angles (Φ/Ψ).
• Validation through molecular dynamics simulations of disaccharides against experimental data (crystal cell parameters, densities, NMR coupling constants).

Main Results:

• New CHARMM force field parameters developed for 1→1, 1→2, 1→3, 1→4, and 1→6 hexopyranose glycosidic linkages and O-methylation.
• Parameters show good agreement with experimental data for disaccharides, validating their accuracy.
• The extended force field accurately models linear, branched, and cyclic hexopyranose glycosides.

Conclusions:

• The newly developed CHARMM force field parameters enable accurate molecular dynamics simulations of hexopyranose polysaccharides.
• These parameters facilitate the study of carbohydrates in isolation and in complex biological environments.
• This advancement enhances the capability to model glycosidic-linked carbohydrates within CHARMM all-atom biomolecular simulations.