Conformation, flexibility and hydration of hyaluronic acid by molecular dynamics simulations.

Hyaluronic acid (HA) is a biopolymer of disaccharide with two alternate glycosidic bonds, β(1,3) and β(1,4). A molecular dynamics study 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. Crossover from a rod-like to a random-coil conformation is observed with increasing the chain length. The conformation with the β(1,4) linkage is more flexible 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. The hydration per disaccharide unit remains constant with the chain length.