Structure and hydration property of low molecular weight hyaluronic acid by molecular dynamics simulations

Abstract

Hyaluronic acid (HA) is a biopolymer of disaccharide with two alternate glycosidic bonds, β(1,3) and β(1,4). It has a wide-range of applications in medicine, nutrition and cosmetics. A molecular dynamics (MD) study in aqueous condition presented here unveiled conformational variability in association with the flexibility of the glycosidic linkers, which depends on the number of disaccharide units. HA chain maintains a rigid rod-like conformation with short chain lengths i.e. with 1 to 10 disaccharide units. Crossover from a rod-like to a random-coil conformation is observed with increasing the chain length i.e. with 20-50 disaccharide units. MD and DFT calculations demonstrated that a disaccharide unit with the β(1,4) linkage has more conformational flexibility than that with the β(1,3) linkage. Variation of the radius of gyration and conformational fluctuation showed that the β(1,4) linkers along with the HA chain length enhance the overall conformational flexibility and therefore elastic response of the polymer chain. Besides the inter-saccharide hydrogen bonding, Na+ binds preferably at the β(1,4) site. The hydration number of HA increases as an increase in the chain length while the hydration per disaccharide unit remains constant with the chain length. Moreover, free energy calculations indicated an energy barrier for HA transferring across biological membranes.