Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process?

ABSTRACT: The prevailing current view of protein folding is the thermodynamic hypothesis, under which the native folded conformation of a protein corresponds to the global minimum of Gibbs free energy G. We question this concept and show that the empirical evidence behind the thermodynamic hypothesis of folding is far from strong. Furthermore, physical theory-based approaches to the prediction of protein folds and their folding pathways so far have invariably failed except for some very small proteins, despite decades of intensive theory development and the enormous increase of computer power. The recent spectacular successes in protein structure prediction owe to evolutionary modeling of amino acid sequence substitutions enhanced by deep learning methods, but even these breakthroughs provide no inf

SUBMITTER: Sorokina I 

PROVIDER: S-EPMC8745595 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature