Large gain in translational entropy of water is a major driving force in protein folding

A view lacking in earlier studies on protein folding is that the process is critically influenced by the thermal motion of water molecules. Here it is pointed out that there is a powerful driving force, a large gain in the translational entropy (TE) of water, which competes with the large loss of the conformational entropy in the folding. We analyze the TE of water in which a protein molecule with a prescribed conformation is immersed. We consider a number of conformations and show that the largest TE is attained only in the native structure.