Analysis of Two-State Folding Using Parabolic Approximation IV: Non-Arrhenius Kinetics of FBP28 WW Part-II

摘要

A model which treats the denatured and the native conformers as beingconfined to harmonic Gibbs energy wells has been used to rationalize thephysical basis for the non-Arrhenius behaviour of spontaneously-folding fixedtwo-state systems. It is shown that at constant pressure and solventconditions: (i) the rate constant for folding will be a maximum when the heatreleased upon formation of net molecular interactions is exactly compensated bythe heat absorbed to desolvate net polar and non-polar solvent accessiblesurface area (SASA), as the denatured conformers driven by thermal noise burytheir SASA and diffuse on the Gibbs energy surface to reach the activatedstate; (ii) the rate constant for unfolding will be a minimum when the heatabsorbed by the native conformers to break various net backbone and sidechaininteractions is exactly compensated by the heat of hydration released due tothe net increase in SASA, as the native conformers unravel to reach theactivated state; (iii) the activation entropy for folding will be zero, and theGibbs barrier to folding will be a minimum, when the decrease in the backboneand the sidechain mobility is exactly compensated by the increase in entropydue to solvent-release, as the denatured conformers bury their SASA to reachthe activated state; and (iv) the activation entropy for unfolding will bezero, and the Gibbs barrier to unfolding will be a maximum when the increase inthe backbone and sidechain mobility is exactly compensated by the negentropy ofsolvent capture on the protein surface, as the native conformers unravel toreach the activated state.