  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.
