title: Theory of protein folding: the energy landscape perspective.
abstract: The energy landscape theory of protein folding is a statistical description of a protein's potential surface. It assumes that folding occurs through organizing an ensemble of structures rather than through only a few uniquely defined structural intermediates. It suggests that the most realistic model of a protein is a minimally frustrated heteropolymer with a rugged funnel-like landscape biased toward the native structure. This statistical description has been developed using tools from the statistical mechanics of disordered systems, polymers, and phase transitions of finite systems. We review here its analytical background and contrast the phenomena in homopolymers, random heteropolymers, and protein-like heteropolymers that are kinetically and thermodynamically capable of folding. The connection between these statistical concepts and the results of minimalist models used in computer simulations is discussed. The review concludes with a brief discussion of how the theory helps in the interpretation of results from fast folding experiments and in the practical task of protein structure prediction.
authors.affiliation: Department of Physics, University of California at San Diego, La Jolla 92093-0319, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Onuchic
authors.forename: Z
authors.initials: Z
authors.lastname: Luthey-Schulten
authors.forename: P G
authors.initials: PG
authors.lastname: Wolynes
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011108:Polymers; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
chemical_list: D011108:Polymers