On the physics of pressure denaturation of proteins

We show that the entropic effect originating from the translational movement of water molecules plays critical roles in the pressure-induced denaturation of proteins. In our statistical–mechanical method, the partial molar volume governing the pressure dependence of the structural stability is expressed in terms of the two geometric measures of each protein structure, the excluded volume and the accessible surface area for water molecules, and a parameter related to the water-density profile entropically formed near its surface. An unfolded structure, which is shown to turn more stable than the native one at an elevated pressure, successfully features the experimentally observed denaturation.