PT - JOURNAL ARTICLE AU - Robert S. Sade TI - Analysis of Two-State Folding Using Parabolic Approximation III: Non-Arrhenius Kinetics of FBP28 WW Part-I AID - 10.1101/038331 DP - 2016 Jan 01 TA - bioRxiv PG - 038331 4099 - http://biorxiv.org/content/early/2016/01/31/038331.short 4100 - http://biorxiv.org/content/early/2016/01/31/038331.full AB - A model which treats the denatured and the native conformers as being confined to harmonic Gibbs energy wells has been used to analyse the non-Arrhenius behaviour of spontaneously-folding fixed two-state systems. The results demonstrate that when pressure and solvent are constant: (i) a two-state system is physically defined only for a finite temperature range; (ii) irrespective of the primary sequence, the 3-dimensional structure of the native conformer, the residual structure in the denatured state, and the magnitude of the folding and unfolding rate constants, the equilibrium stability of a two-state system is a maximum when its denatured conformers bury the least amount of solvent accessible surface area (SASA) to reach the activated state; (iii) the Gibbs barriers to folding and unfolding are not always due to the incomplete compensation of the activation enthalpies and entropies; (iv) the difference in heat capacity between the reaction-states is due to both the size of the solvent-shell and the non-covalent interactions; (v) the position of the transition state ensemble along the reaction coordinate (RC) depends on the choice of the RC; and (vi) the atomic structure of the transiently populated reaction-states cannot be inferred from perturbation-induced changes in their energetics.