MOLECULAR-DYNAMICS SIMULATION OF OLIGOSACCHARIDES CONTAINING N-ACETYLNEURAMINIC ACID

Alpha-N-acetyl neuraminic acid (Neu5Ac, sialic acid) is a commonly occ urring carbohydrate residue in various cell surface glycolipids and gl ycoproteins. This residue is linked terminally or internally to Gal re sidues via an alpha(2 --> 3) or alpha(2 --> 6) linkage. In the cell su rface receptor, sialyl-Lewis(X), a terminal alpha(2 --> 3) linkage is present. Previous studies from our laboratory have shown that in solut ion Lewis(X) adopts a relatively rigid structure. In order to model th e Neu5Ac residue, vacuum molecular dynamics of this monosaccharide wer e compared with simulations that explicitly include solvent water. The dynamical average of the monosaccharide conformation obtained from th e two simulations was similar. Vacuum calculations for the disaccharid e Neu5Ac alpha(2 --> 3) Gal beta-O-methyl show that a number of low en ergy minima are accessible to this disaccharide. Molecular dynamics si mulations starting from the low energy minima show conformational tran sitions with a time scale of 10-50 ps among several of the minima whil e large barriers between other minima prevent transitions on the time scale studied. Simulations of this disaccharide in the presence of sol vent show fewer conformational transitions, illustrating a dampening e ffect of the solvent that has been observed in some other studies. Our results are most consistent with an equilibrium among multiple confor mations for the Neu5Ac alpha(2 --> 3) Gal beta linkage. (C) 1994 John Wiley & Sons, Inc.