The conformations of the oligosaccharides are being studied by the molecular dynamics (MD) simulations and compared to, where ever known, with the conformations of the oligosaccharide in the protein-carbohydrate crystal complexes.
The aim i s to present a stereochemical explanation of the observed structures in the crystal of lectin-oligosaccharide complexes and also reveal the range of conformations an oligosaccharide can access, the information which is vital for understanding carbohydrate protein interactions. Initially, conformations of the heptasaccharide moiety of Erythrina corallodendron Lectin (EcorL), Man-alpha1,6-(Manalpha1,3)(Xylbeta1,2)- Manbeta1,4-GlcNAc2beta beta1,4-(L-Fucalpha1,3)-GlcNAc1, the hexasaccharide Manalpha1,6alpha(Manalpha,3)(GlcNAc- beta1,4)- Manbeta1,4-GlcNAcbeta1,4-GlcNAc and their disaccharide fragments were studied by molecular dynamics (MD) simulations for 1000 ps with different initial conformations. These conformations were compared with the conformation of the heptasaccharide in the crystal structure of EcorL complexed with the oligosaccharide. The conformation of the heptasaccharide found in the crystal structure of the EcorL-lactose complex, that has a psi value of about 76 degree0 around Man-1,6-Man linkage, is accessed, though less frequently, during MD of the isolated oligosaccharide. These psi values for the alpha1,6 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. These results showed that the less frequently accessed conformation of the heptasaccharide during MD simulations presents a better complementary surface to bind to the symmetry related lectin molecule in the crystal. If the heptasaccharide is not in this conformation while initiating the binding process, the conformation around Man6alpha1,6-Manm will be altered by changing psi to provide better complementary surface and to form additional hydrogen bonds with the protein at the expense of internal hydrogen bonds. Currently, several other high mannose oligosacchairde -protein complexes, and galactose and lactose bound protein complexes are being investigated.
