Water-mediated biomolecular dynamics and allostery
David M. Leitner, Changbong Hyeon, Korey M. Reid
Abstract
Dynamic coupling with water contributes to regulating the functional dynamics of a biomolecule. We discuss protein–water dynamics, with emphasis on water that is partially confined, and the role of protein-confined water dynamics in allosteric regulation. These properties are illustrated with two systems, a homodimeric hemoglobin from Scapharca inaequivalvis (HbI) and an A2A adenosine receptor (A2AAR). For HbI, water–protein interactions, long known to contribute to the thermodynamics of cooperativity, are seen to influence the dynamics of the protein not only around the protein–water interface but also into the core of each globule, where dynamic and entropic changes upon ligand binding are coupled to protein–water contact dynamics. Similarly, hydration waters trapped deep inside the core region of A2AAR enable the formation of an allosteric network made of water-mediated inter-residue contacts. Extending from the ligand binding pocket to the G-protein binding site, this allosteric network plays key roles in regulating the activity of the receptor.