Thermodynamic Principle Revisited: Theory of Protein Folding

Abstract

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 () X; , N G U E , 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 () X; , N G U E 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.

Single Molecule Thermodynamics Hypothesis of Protein Folding and Drug Design

“…That law is the Thermodynamic Principle of Protein Folding [1], it is just the Second Law of Thermodynamics since Anfinsen and others already shown that the folding process is spontaneous. In the protein folding case, the second law is that the Gibbs free Via quantum statistics applied to a tiny thermodynamic system X S which is tailor made for the conformation X and its immediate physiological environment U E , we have derived the conformational Gibbs free energy (CGFE) function ( ; , ) G X U E U for globular proteins U 4].…”