Effect of solvent and ions on the structure and dynamics of a hyaluronan molecule

Hyaluronic acid (hyaluronan, HA) is a negatively charged polysaccharide forming highly swollen random coils in aqueous solutions. Their size decreases along with growing salt concentration, but the mechanism of this phenomenon remains unclear. We carry out molecular-dynamics simulations of a 48-monosaccharide HA oligomer in varying salt concentration and temperature. They identify the interaction points of Na+ ions with the HA chain and reveal their influence on the HA solvation-shell structure. The salt-dependent variation of the molecular size does not consist in the distribution of the dihedral angles of the glycosidic connections but is driven by the random flips of individual dihedral angles, which cause the formation of temporary hairpin-like structures effectively shortening the chain. They are induced by the frequency of cation-chain interactions that grow with the salt concentration, but is reduced by the simultaneous decrease of ions’ activities. This leads to an anomalous random-coil shrinkage at 0.6 M salt concentration. © 2020 The AuthorsInternal Funding Agency of Tomas Bata University in Zlin [IGA/FT/2016/011, IGA/FT/2017/009, IGA/FT/2018/010]; Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P208-12-G016