The protein–solvent interface: a big splash

Abstract

Water plays many roles in its interaction with water–soluble proteins through hydrogen bonding, electrostatic shielding and the hydrophobic effect. Water molecules are found on the surface of proteins, in clefts and channels and in cavities buried beneath the surface. We review data on these relating to structure, thermodynamics, dynamics and function. At interfaces, water may play two roles. Firstly, the absence of solvent may contribute to the favourable free energy of binding. Secondly, the presence of solvent may control the level of specificity or contribute to a favourable enthalpy. Finally, we review the role of solvent in unfolding proteins and the relation of protein unfolding/misfolding to disease.