title: A metastable state in folding simulations of a protein model.
abstract: The native state of a protein is generally believed to be the global free energy minimum. However, there is increasing evidence that kinetically selected states play a role in the biological function of some proteins. In a recent folding study of a 125-residue heteropolymer model, one of 200 sequences was found to fold repeatedly to a particular local minimum that did not interconvert to the global minimum. The kinetic preference for this 'metastable' state is shown to derive from an entropic barrier associated with inserting a tail segment into the protein interior of the serpin-like global minimum structure. The relation of the present results to the role of metastable states in functioning and pathogenic proteins is discussed.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Dinner
authors.forename: M
authors.initials: M
authors.lastname: Karplus
mesh_terms: D003198:Computer Simulation; D004355:Drug Stability; D019277:Entropy; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins