Hydration as a major factor in preferential solvent-protein interactions

It has been well-documented that polar groups on the surface of proteins have water molecules tightly bound to them; that is to say, proteins are hydrated in aqueous solution. If this hydration is maintained in a concentrated solution of a cosolute, a difference in the concentration of the cosolute develops between the bulk solution and the vicinity of the protein, resulting in preferential hydration such that excess water accumulates near the protein under dialysis equilibrium. This preferential hydration leads to cosolute-induced stabilization and salting-out of the protein in concentrated solutions of the cosolute. Preferential binding of the cosolute occurs when it binds to the protein at a level at which the concentration of the cosolute in the vicinity of the protein exceeds the concentration of the cosolute in bulk solution. When binding of the cosolute reaches saturation, a constant level of hydration (physically bound water) can lead to preferential hydration of the protein at higher concentrations of the cosolute.