title: 5 nanosecond molecular dynamics and NMR study of conformational transitions in the sialyl-Lewis X antigen.
abstract: The range of internal motions of the sialyl Lewis-X (SLe(x)) tetrasaccharide (NeuNAc alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc) [where Fuc is L-fucopyranose, Gal is D-galactopyranose, GlcNAc is 2-acetamido-2-deoxy-D-glucopyranose and NeuNAc is D-neuraminic acid (sialic acid)] was studied by restrained simulated annealing and restrained molecular dynamics (MD) calculations. Transitions between predominantly two conformational states were observed for the NeuNAc alpha (2-->3)Gal linkage, consistent with previous observations for this linkage in sialyl-N-acetyllactosamine. The MD trajectory was simulated for 5 ns of real time, in order to observe a statistically significant number of these relatively low-frequency transitions. The Fuc alpha(1-->3)GlcNAc and Gal beta (1-->4)GlcNAc linkages, however, showed more restricted flexibility within a single energy well (RMS differences for the time-averaged glycosidic torsion angles, <phi> and <psi>, were 50% lower than for the NeuNAc alpha(2-->3)Gal linkage), and approximate to a rigid conformation. NMR parameters [relative rotating-frame Overhauser enhancement (r.O.e.) and inter-glycosidic 3JCH] back-calculated from the MD simulation were in close agreement with experimentally measured values for the free reducing oligosaccharide in D2O solution.
authors.affiliation: Department of Biochemistry, University of Dundee, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: D G
authors.initials: DG
authors.lastname: Spackman
authors.forename: P J
authors.initials: PJ
authors.lastname: Simpson
authors.forename: S W
authors.initials: SW
authors.lastname: Homans
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D007519:Isoantigens / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen
chemical_list: D007519:Isoantigens; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen