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Dominant Pathways in Protein Folding

P. Faccioli·M. Sega·F. Pederiva·H. Orland
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Abstract

We present a method to investigate the kinetics of protein folding on a long time-scale and the dynamics underlying the formation of secondary and tertiary structures during the entire reaction. The approach is based on the formal analogy between thermal and quantum diffusion: by writing the solution of the Fokker-Planck equation for the time-evolution of a protein in a viscous heat-bath 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, in the framework of a Go-model. We have found that, in this model, the transition occurs through an initial collapsing phase driven by the starting coil configuration and a later rearrangement phase, in which secondary structures are formed and all computed paths display strong similarities. This method is completely general, does not require the prior knowledge of any reaction coordinate and represents an efficient tool to perfom ab-initio simulations of the entire folding process with available computers.

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P. Faccioli, M. Sega, F. Pederiva, H. Orland. 2006-07-27. Dominant Pathways in Protein Folding. https://doi.org/10.1103/physrevlett.97.108101

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