Protein Folding: The Gibbs Free Energy

TL;DR

This paper derives a quantum mechanics-based formula for Gibbs free energy in protein folding, explaining key phenomena and providing a foundation for ab initio structure prediction.

Contribution

It presents a quantum statistical derivation of Gibbs free energy for protein conformations, unifying folding and denaturation explanations.

Findings

The formula explains hydrophobic effects and hydrogen bonding roles.

It clarifies surface area model successes and limitations.

Provides a basis for ab initio protein structure prediction.

Abstract

The fundamental law for protein folding is the Thermodynamic Principle: the amino acid sequence of a protein determines its native structure and the native structure has the minimum Gibbs free energy. If all chemical problems can be answered by quantum mechanics, there should be a quantum mechanics derivation of Gibbs free energy formula G(X) for every possible conformation X of the protein. We apply quantum statistics to derive such a formula. For simplicity, only monomeric self folding globular proteins are covered. We point out some immediate applications of the formula. We show that the formula explains the observed phenomena very well. It gives a unified explanation to both folding and denaturation; it explains why hydrophobic effect is the driving force of protein folding and clarifies the role played by hydrogen bonding; it explains the successes and deficients of various surface area models. The formula also gives a clear kinetic force of the folding: Fi(X) = - \nablaxi G(X). This also gives a natural way to perform the ab initio prediction of protein structure, minimizing G(X) by Newton's fastest desciending method.