In-silico investigation of the conformational properties of the disaccharide units of chondroitin, dermatan and heparan sulphate in aqueous medium

Abstract

Atomistic molecular dynamics simulations were performed for the aqueous solutions of the disaccharide building blocks of chondrotin sulphate (CS), dermatan sulphate (DS) and heparan sulphate (HS) with the sulphation done at 4/3 and 6 positions of the GalNAc/GlcNAc unit of the molecules to explore the conformational properties of the molecules and the effects of sulphation on them. Heterogeneous conformational flexibilities of the disaccharide building blocks of the molecules arising from the –OH and -SO3 groups were observed to play role in the overall flexibilities of the molecules. Ring and dihedral angle rotation involving glycoside bond was observed to have different effects on the conformational properties of the three studied molecules. 1H and 13C chemical shift for the molecules as computed by using Quantum mechanical approach was observed to be increased with the increase of the sulphation in the molecules. Sulphation was also noticed to have important contribution towards the formation of GAG-water hydrogen bonds and the conformational flexibilities of the molecules.