Effect of heavy water on the conformational stability of globular proteins.

It is well established from the experimental point of view that the native state of globular proteins is more stable in heavy water than in water. No robust explanation, however, has been provided up to now. The application of the theoretical approach, originally devised to rationalize the general occurrence of cold denaturation, indicates that the magnitude of the solvent-excluded volume effect is slightly smaller in heavy water than in water and cannot explain the observed protein stabilization. The latter has to be due to the strength of protein-water van der Waals attractions which are weaker in heavy water due to the smaller molecular polarizability of D O compared with that of H O molecules. Since protein-water van der Waals attractions occur more in the denatured than in the native state, this contribution leads to a stabilization of the latter through a destabilization of the former.