Molecular dynamics simulations of oligosaccharides and their conformation in the crystal structure of lectin-carbohydrate complex: importance of the torsion angle psi for the orientation of alpha 1,6-arm.

The conformation of the heptasaccharide Man-alpha 1,6-(Man-alpha 1,3)(Xyl-beta 1,2)-Man-beta 1,4-GlcNAc2-beta 1,4-(L- Fuc-alpha 1,3)-GlcNAc1, the carbohydrate moiety of Erythrina corallodendron lectin (EcorL), the hexasaccharide Man-alpha 1,6-(Man-alpha 1,3) (GlcNAc-beta 1,4)-Man-beta 1,4-GlcNAc-beta 1,4-GlcNAc and their disaccharide fragments have been studied by molecular dynamics (MD) simulations for 1000 ps with different initial conformations. In the isolated heptasaccharide, the most frequently accessed conformation during MD has a psi value of 180 degrees around Man-alpha 1,6-Man linkage. This conformation is stabilized by the formation of a hydrogen bond between the carbonyl oxygen of GlcNAc2 with the O3/O4 hydroxyls of the alpha 1,6-linked mannose residue. The conformation of the heptasaccharide found in the crystal structure of the EcorL-lactose complex (Shaanan et al., Science, 254, 862, 1991), that has a psi value of approximately 76 degrees around Man-alpha 1,6-Man linkage, is accessed, although less frequently, during MD of the isolated oligosaccharide. The phi, psi, chi = 58 degrees, -134 degrees, -60 degrees conformation around Man-alpha 1,6-Man fragment observed in the crystal structure of the Lathyrus ochrus lectin complexed with a biantennary octasaccharide (Table I in Homans, S.W., Glycobiology, 3, 551, 1993) has also been accessed in the present MD simulations. These psi values for the alpha 1,6-linkage, which are observed in the protein-carbohydrate crystal structures and are accessed in the MD simulations, though occasionally, have not been predicted from NMR studies. Furthermore, these different values of psi lead to significantly different orientations of the alpha 1,6-arm for the same value of chi. This contrasts with the earlier predictions that only different values of chi can bring about significant changes in the orientation of the alpha 1,6-arm. The MD simulations also show that the effects of bisecting GlcNAc or beta 1,2-xylose are very similar on the alpha 1,3-arm and slightly different on the alpha 1,6-arm.