500-Picosecond Molecular Dynamics in Water of the Mana 1-2Mana Glycosidic Linkage Present in Asn-Linked Oligomannose-Type Structures on Glycoproteins+

ABSTRACT: Molecular dynamics simulations of the M a n a 1-2Mana glycosidic linkage found in the N-linked glycans of glycoproteins were performed in vacuo and in the presence of water. In the latter case significant dampening of the molecular fluctuations was found when compared to the in vacuo simulation. A 500-ps dynamics simulation in water showed only occasional short-lived deviations from the minimum-energy conformation, more consistent with carbohydrate “breathing ” than flexibility. These studies add further evidence that oligosaccharides can maintain “fixed ” geometries with relatively long lifetimes and a re in agreement with experimental NMR-derived parameters for the same linkage in oligomannose structures. M o l e c u l a r dynamics is a well-established method for the investigation of the conformational behavior of the protein part of glycoproteins and DNA [McCammon et al. (1987) and references cited therein]. These studies have been conducted both in vacuo and in various solvents and have contributed greatly to the understanding of the exact nature of the sub-stantial structural fluctuations that may occur in such mole-cules. Experimentally, such fluctuations have been shown t