The Broken Symmetry of Low Temperature and High Temperature Unfolding of Proteins in Water

We consider a very simple mathematical model of the thermodynamic stability of globular proteins in water at high and low temperatures, stressing the concepts of broken symmetry in the water-protein system. There are two crucial concepts: 1) The continuum of conformations that a protein can have when dissolved in water; 2) The broken symmetry of the order parameter of the packing density of the amino acids at high and low temperatures. Using simple thermodynamic arguments we make predictions about two basic instability regions of a protein at both high and low temperatures. For widely satisfied parametric conditions, we demonstrate the existence of a unique cold denaturation temperature related to the hot denaturation temperature. We point out that there exists some confusion in the literature concerning this thermodynamic analysis, which we clarify in our exact solution. We finally discuss new experimental technologies which could explore thermal stability range of proteins.