Conformational flexibility of a protein–carbohydrate complex and the structure and ordering of surrounding water

Protein–carbohydrate non-covalent interactions are important to understand various biological processes in living organisms. One of the important issues in protein–carbohydrate binding is how the protein identifies the target carbohydrate and recognizes its conformational features. Surrounding water molecules are expected to play a critical role not only in mediating the recognition process but also in maintaining the structure of the complex. We carried out atomistic molecular dynamics (MD) simulations of an aqueous solution of the protein–carbohydrate complex formed between the hyaluronan binding domain (HABD) of the murine Cd44 protein and the octasaccharide hyaluronan (HA8). The conformational flexibilities of the protein and the carbohydrate, and the microscopic structure and ordering of water molecules around them in the complexed form have been explored. It is revealed that the formation of the complex is associated with significant immobilization of the monosaccharide units of the carbohydrate moiety that are involved in binding. Further, reduction in water densities around the binding residues of the two molecules in the complex with respect to their free forms clearly demonstrated that the recognition between the protein and the carbohydrate is facilitated by removal of a fraction of water molecules from regions around the binding domains.