RT Journal Article
SR Electronic
T1 Analysis of Two-State Folding Using Parabolic Approximation I: Hypothesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 036491
DO 10.1101/036491
A1 Robert S. Sade
YR 2016
UL http://biorxiv.org/content/early/2016/01/31/036491.abstract
AB A model which treats the denatured and native conformers of spontaneously-folding fixed two-state systems as being confined to harmonic Gibbs energy-wells has been developed. Within the assumptions of this model the Gibbs energy functions of the denatured (DSE) and the native state (NSE) ensembles are described by parabolas, with the mean length of the reaction coordinate (RC) being given by the temperature-invariant denaturant m value. Consequently, the ensemble-averaged position of the transition state ensemble (TSE) along the RC, and the ensemble-averaged Gibbs energy of the TSE are determined by the intersection of the DSE and the NSE-parabolas. The equations derived enable equilibrium stability and the rate constants to be rationalized in terms of the mean and the variance of the Gaussian distribution of the solvent accessible surface area of the conformers in the DSE and the NSE. The implications of this model for protein folding are discussed.