Solution conformations of a trimannoside from nuclear magnetic resonance and molecular dynamics simulations

N-linked oligosaccharides often act as ligands for receptor proteins in a variety of cell recognition processes. Knowledge of the solution conformations, as well as protein-bound conformations, of these oligosaccharides is required to understand these important interactions. In this paper we present a model for the solution conformations sampled by a simple trimannoside, methyl 3,6-di-O-(alpha -D-mannopyranosyl)-alpha -D-mannopyranoside which contains two of the most commonly found glycosidic linkages in N-linked oligosaccharides. This model was derived from simulated annealing protocols incorporating distance restraints extracted from NOESY spectra along with torsional restraints computed from three-bond H-1-C-13 coupling constants measured across the glycosidic bonds. The model was refined in light of unrestrained molecular dynamics simulations conducted in the presence of solvent water. The resulting model depicts a molecule undergoing conformational averaging in solution, adopting four major and two minor conformations. The four major conformations arise from a pair of two-state transitions, one each at the alpha (1-->3) and alpha (1-->6) linkages, whereas the minor conformations result from an additional transition of the alpha (1-->6) linkage. Our data also suggest that the alpha (1-->3) transition is fast and changes the molecular shape slightly, whereas the alpha (1-->6) is much slower and alters the molecular shape dramatically.