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 λ-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.
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15 March 2001
Research Article|
March 15 2001
Microscopic theory of protein folding rates. I. Fine structure of the free energy profile and folding routes from a variational approach
John J. Portman;
John J. Portman
Department of Physics, University of Illinois, Urbana, Illinois 61801
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Shoji Takada;
Shoji Takada
Department of Chemistry, Kobe University, Kobe 657-8501, Japan
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Peter G. Wolynes
Peter G. Wolynes
Department of Chemistry, University of Illinois, Urbana, Illinois 61801
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J. Chem. Phys. 114, 5069–5081 (2001)
Article history
Received:
August 31 2000
Accepted:
October 30 2000
Connected Content
A companion article has been published:
Microscopic theory of protein folding rates. II. Local reaction coordinates and chain dynamics
Citation
John J. Portman, Shoji Takada, Peter G. Wolynes; Microscopic theory of protein folding rates. I. Fine structure of the free energy profile and folding routes from a variational approach. J. Chem. Phys. 15 March 2001; 114 (11): 5069–5081. https://doi.org/10.1063/1.1334662
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