title: Molecular dynamics simulation of oligosaccharides containing N-acetyl neuraminic acid.
abstract: alpha D-N-acetyl neuraminic acid (Neu5Ac, sialic acid) is a commonly occurring carbohydrate residue in various cell surface glycolipids and glycoproteins. This residue is linked terminally or internally to Gal residues via an alpha(2-->3) or alpha(2-->6) linkage. In the cell surface receptor, sialyl-LewisX, a terminal alpha(2-->3) linkage is present. Previous studies from our laboratory have shown that in solution LewisX adopts a relatively rigid structure. In order to model the Neu5Ac residue, vacuum molecular dynamics of this monosaccharide were compared with simulations that explicitly include solvent water. The dynamical average of the monosaccharide conformation obtained from the two simulations was similar. Vacuum calculations for the disaccharide Neu5Ac alpha(2-->3) Gal beta-O-methyl show that a number of low energy minima are accessible to this disaccharide. Molecular dynamics simulations starting from the low energy minima show conformational transitions with a time scale of 10-50 ps among several of the minima while large barriers between other minima prevent transitions on the time scale studied. Simulations of this disaccharide in the presence of solvent show fewer conformational transitions, illustrating a dampening effect of the solvent that has been observed in some other studies. Our results are most consistent with an equilibrium among multiple conformations for the Neu5Ac alpha(2-->3) Gal beta linkage.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County 21228.
authors.forename: C
authors.initials: C
authors.lastname: Mukhopadhyay
authors.forename: C A
authors.initials: CA
authors.lastname: Bush
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000737:chemistry; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D009844:Oligosaccharides / Q000737:chemistry*; D012794:Sialic Acids / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid