title: Theory of kinetic partitioning in protein folding with possible applications to prions.
abstract: This study focuses of the phenomenon of kinetic partitioning when a polypeptide chain has two ground-state conformations, one of which is kinetically more reachable than the other. We designed sequences for lattice model proteins with two different conformations of equal energy corresponding to the global energy minimum. Folding simulations revealed that one of these conformations was indeed much more kinetically accessible than the other. We found that the number and strength of local contacts in the ground-state conformation are the major factors that determine which conformation is reached faster; the greater the number of local contacts, the more kinetically reachable a conformation is. We present simple statistical-mechanical arguments to explain these findings. Our results may be relevant in explaining the phenomenology of such proteins as human plasminogen activator inhibitor-1 (PAI-1), photosystem II, and prions.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: V I
authors.initials: VI
authors.lastname: Abkevich
authors.forename: A M
authors.initials: AM
authors.lastname: Gutin
authors.forename: E I
authors.initials: EI
authors.lastname: Shakhnovich
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry; D018621:PrPC Proteins / Q000737:chemistry; D018620:PrPSc Proteins / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics
chemical_list: D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions