Molecular Dynamics Simulation Studies on Sialic Acid and Its Acetylated Derivatives and Their Interaction with Vibrio Cholerae Neuraminidase

摘要

Sialic acids are 9- carbon acid sugars, in which structural diversity is generated by various substitution such as acetylation, methylation, sulfation and lactlylation at 4, 5, 7,8 and 9- carbon positions. Molecular Dynamics simulation of 10ns duration was carried out for Sialic acid and its acetylated derivatives to study the conformational aspects of acetamido, glycerol and acetyl group. The glycerol side chain conformation of sialic acid and its acetylated derivatives are stabilized by the water mediated hydrogen bonding interaction between O8/O9 hydroxyl and carboxylic acid group. More conformational flexibility is observed for 4-O-acetyl group when compared with the acetylated group of the glycerol side chain in sialic acid. The cleavage of sialic acid by Vibrio Cholerae Neuraminidase (VCN) especially shows the dependency of the acetylation at the various positions of the hydroxyl groups. The spatial flexibility of sialic acid and its acetylated derivatives at the binding site of VCN indicated two permissible allowed eulerian regions. However VCN can accommodate the oligosaccharides in one eulerian region. The spatial flexibility of sialic acid and its acetylated derivatives at the binding pocket of Vibrio Cholerae Neuraminidase was correlated to the cleavage specificity.