Molecular origin of the cosolvent-induced changes in the thermal stability of proteins

Various cosolvents are known to modulate the thermal stability of the proteins. To understand its molecular origin, a statistical thermodynamic analysis, based upon the Kirkwood–Buff (KB) theory, has been performed to obtain information regarding the accumulation or depletion of solvent molecules around proteins, based upon published experimental data. The analysis shows the dominant importance of cosolvent’s accumulation or depletion around the proteins, whereas the role of protein hydration is minor.