Two State Behavior in a Solvable Model of ${\hat{I}}^2$-hairpin folding

Abstract

Understanding the mechanism of protein secondary structure formation is an essential part of protein-folding puzzle. Here we describe a simple model for the formation of the ${\hat{I}}^2$-hairpin, motivated by the fact that folding of a ${\hat{I}}^2$-hairpin captures much of the basic physics of protein folding. We argue that the coupling of ``primary'' backbone stiffness and ``secondary'' contact formation (similar to the coupling between the ``secondary'' and ``tertiary'' structure in globular proteins), caused for example by side-chain packing regularities, is responsible for producing an all-or-none 2-state ${\hat{I}}^2$-hairpin formation. We also develop a recursive relation to compute the phase diagram and single exponential folding/unfolding rate arising via a dominant transition state.

Revised version