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    Dominant Pathways in Protein Folding

    P. Faccioli1,2, M. Sega3, F. Pederiva4, and H. Orland5

    • 1Dipartimento di Fisica Universitá degli Studi di Trento e I.N.F.N, Via Sommarive 14, Povo (Trento), I-38050 Italy
    • 2European Centre for Theoretical Studies in Nuclear Physics and Related Areas (E.C.T.*), Strada delle Tabarelle 284, Villazzano (Trento), I-38050 Italy
    • 3C.N.R./I.N.F.M. and Dipartimento di Fisica, Universitá degli Studi di Trento, Via Sommarive 14, Povo (Trento), I-38050 Italy
    • 4Dipartimento di Fisica and C.N.R./I.N.F.M.-DEMOCRITOS National Simulation Center, Universitá degli Studi di Trento, Via Sommarive 14, Povo (Trento), I-38050 Italy
    • 5Service de Physique Théorique, Centre d’Etudes de Saclay, F-91191, Gif-sur-Yvette Cedex, France

    Phys. Rev. Lett. 97, 108101 – Published 6 September, 2006

    DOI: https://doi.org/10.1103/PhysRevLett.97.108101

    Abstract

    We present a method to investigate the kinetics of protein folding and the dynamics underlying the formation of secondary and tertiary structures during the entire reaction. By writing the solution of the Fokker-Planck equation in terms of a path integral, we derive a Hamilton-Jacobi variational principle from which we are able to compute the most probable pathway of folding. The method is applied to the folding of the Villin headpiece subdomain simulated using a Go model. An initial collapsing phase driven by the initial configuration is followed by a rearrangement phase, in which secondary structures are formed and all computed paths display strong similarities. This completely general method does not require the prior knowledge of any reaction coordinate and is an efficient tool to perform simulations of the entire folding process with available computers.

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