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Microscopic theory of protein folding rates. II. Local reaction coordinates and chain dynamics
The motions involved in barrier crossing for protein folding are investigated in terms of the chain dynamics of the polymer backbone, completing the microscopic description of protein folding presente...

Microscopic theory of protein folding rates. I. Fine structure of the free energy profile and folding routes from a variational approach

J. Chem. Phys. 114, 5069 (2001); doi:10.1063/1.1334662

Issue Date: 15 March 2001

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John J. Portman
Department of Physics, University of Illinois, Urbana, Illinois 61801

Shoji Takada
Department of Chemistry, Kobe University, Kobe 657-8501, Japan

Peter G. Wolynes
Department of Chemistry, University of Illinois, Urbana, Illinois 61801
A microscopic theory of the free energy barriers and folding routes for minimally frustrated proteins is presented, greatly expanding on the presentation of the variational approach outlined previously [J. J. Portman, S. Takada, and P. G. Wolynes, Phys. Rev. Lett. 81, 5237 (1998)]. We choose the lambda-repressor protein as an illustrative example and focus on how the polymer chain statistics influence free energy profiles and partially ordered ensembles of structures. In particular, we investigate the role of chain stiffness on the free energy profile and folding routes. We evaluate the applicability of simpler approximations in which the conformations of the protein molecule along the folding route are restricted to have residues that are either entirely folded or unfolded in contiguous stretches. We find that the folding routes obtained from only one contiguous folded region corresponds to a chain with a much greater persistence length than appropriate for natural protein chains, while the folding route obtained from two contiguous folded regions is able to capture the relatively folded regions calculated within the variational approach. The free energy profiles obtained from the contiguous sequence approximations have larger barriers than the more microscopic variational theory which is understood as a consequence of partial ordering. ©2001 American Institute of Physics.
History: Received 31 August 2000; accepted 30 October 2000
Permalink: http://link.aip.org/link/?JCPSA6/114/5069/1
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EDITORIALLY RELATED

  1. Microscopic theory of protein folding rates. II. Local reaction coordinates and chain dynamics
    John J. Portman et al.
    J. Chem. Phys. 114, 5082 (2001)

KEYWORDS and PACS

Keywords
PACS
  • 87.14.Ee
    Biological and medical physics Biomolecules: types Proteins
  • 87.15.Cc
    Biological and medical physics Biomolecules: structure and physical properties Folding and sequence analysis
  • YEAR: 2001

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0021-9606 (print)   1089-7690 (online)
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