A STATISTICAL-MECHANICAL MODEL FOR BETA-HAIRPIN KINETICS

Understanding the mechanism of protein secondary structure formation i s an essential part of the protein-folding puzzle. Here, we describe a simple statistical mechanical model for the formation of a beta-hairp in, the minimal structural element of the antiparallel beta-pleated sh eet. The model accurately describes the thermodynamic and kinetic beha vior of a 16-residue, beta-hairpin-forming peptide, successfully expla ining its two-state behavior and apparent negative activation energy f or folding, The model classifies structures according to their backbon e conformation, defined by 15 pairs of dihedral angles, and is further simplified by considering only the 120 structures with contiguous str etches of native pairs of backbone dihedral angles. This single sequen ce approximation is tested by comparison with a more complete model th at includes the 2(15) possible conformations and 15 x 2(15) possible k inetic transitions. Finally, we use the model to predict the equilibri um unfolding curves and kinetics for several variants of the beta-hair pin peptide.