Thermodynamic Principle Revisited: Theory of Protein Folding

Anfinsen’s thermodynamic hypothesis is reviewed and misunderstandings are clarified. It really should be called the thermodynamic principle of protein folding. Energy landscape is really just the mathematical graph of the Gibbs free energy function G(X;U ,EN), a very high dimensional hyper surface. Without knowing it any picture of the Gibbs free energy landscape has no theoretical base, including the funnel shape claims. New insight given by newly obtained analytic Gibbs free energy function G(X;U ,EN) of protein folding derived via quantum statistical mechanics are discussed. Disputes such as target-based or cause-based; what is the folding force, hydrophobic effect or hydrophilic force? Single molecule or ensemble of molecules to be used for the statistical physics study of protein folding, are discussed. Classical observations of 1970’s and 1980’s about global geometric characteristics of native structures of globular proteins turn out to have grabbed the essence of protein folding, but unfortunately have been largely forgotten.