Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling Original Research Article

Explicit-solvent molecular dynamics (MD) simulations of the 11 glucose-based disaccharides in water at 300 K and 1 bar are reported. The simulations were carried out with the GROMOS 45A4 force-field and the sampling along the glycosidic dihedral angles ϕ and ψ was artificially enhanced using the local elevation umbrella sampling (LEUS) method. The trajectories are analyzed in terms of free-energy maps, stable and metastable conformational states (relative free energies and estimated transition timescales), intramolecular H-bonds, single molecule configurational entropies, and agreement with experimental data. All disaccharides considered are found to be characterized either by a single stable (overwhelmingly populated) state ((1→n)-linked disaccharides with n = 1, 2, 3, or 4) or by two stable (comparabl