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Review
. 1999 May 25;96(11):5897-9.
doi: 10.1073/pnas.96.11.5897.

Searching for "downhill scenarios" in protein folding

W A Eaton  1
Affiliations
Review

Searching for "downhill scenarios" in protein folding

W A Eaton. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Figure 1
Figure 1
Schematic of one and two-dimensional free energy surfaces. (Left) Free energy as a function of the fraction of native contacts (Q) and the radius of gyration (Rg). This surface has three significant minima, one for an expanded denatured state (DE), one for a compact denatured state (DC), and one for the native state (N). To simplify the brief discussion of this surface the somewhat unrealistic assumption is made that Q is the same for DE and DC, and Rg is the same for DC and N. For this free energy surface Q may be a good reaction coordinate for forming the native state N from DC or DE, and Rg may be a good reaction coordinate for collapse of the expanded denatured state DE to DC or N, but not vice versa. If so, then the kinetics of folding and unfolding, as well as the kinetics of collapse and expansion of the denatured protein, might be described as diffusion on one-dimensional free energy surfaces (Right).† One of the major outstanding issues is whether DE has a topology that is near native (assumed for a “molten globule”) or is more nearly a “random globule” with a distribution of topologies, in which case DC should be considered a trap on the free energy surface containing misfolded structures. (Upper Right) Free energy as a function of Q for folding over a barrier (continuous blue curve) and for downhill folding (dotted red curve) in a type 0 scenario in the classification of Bryngelson et al. (9). (Lower Right) Free energy as a function of Rg. Submillisecond time-resolved small-angle x-ray scattering experiments are being performed that hold the promise of resolving these kinetics (L. Pollack, M. W. Tate, N. C. Darnton, J. B. Knight, S. M. Gruner, W.A.E., and R. H. Austin, unpublished work).
See this image and copyright information in PMC

Comment on

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