title: Reactive flux and folding pathways in network models of coarse-grained protein dynamics.
abstract: The reactive flux between folded and unfolded states of a two-state protein, whose coarse-grained dynamics is described by a master equation, is expressed in terms of the commitment or splitting probabilities of the microstates in the bottleneck region. This allows one to determine how much each transition through a dividing surface contributes to the reactive flux. By repeating the analysis for a series of dividing surfaces or, alternatively, by partitioning the reactive flux into contributions of unidirectional pathways that connect reactants and products, insight can be gained into the mechanism of protein folding. Our results for the flux in a network with complex connectivity, obtained using the discrete counterpart of Kramers' theory of activated rate processes, show that the number of reactive transitions is typically much smaller than the total number of transitions that cross a dividing surface at equilibrium.
authors.affiliation: Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892, USA. berezh@helix.nih.gov
authors.forename: Alexander
authors.initials: A
authors.lastname: Berezhkovskii
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hummer
authors.forename: Attila
authors.initials: A
authors.lastname: Szabo
mesh_terms: D006801:Humans; D008956:Models, Chemical; D009010:Monte Carlo Method; D055585:Physical Phenomena; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics; D013499:Surface Properties; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D011506:Proteins