C. Snow and V. S. Pande. Biophysical Journal, (2006)
ABSTRACT: Using distributed molecular dynamics simulations we located 4 distinct folding transitions for a 39 residue beta-beta-alpha-beta protein fold. We introduce and sequentially determine the transmission probability, Ptrans, of 500 conformations along each free energy barrier at room temperature, and determined which conformations were transition state ensemble members (Ptrans ≈ 0.5). We ran similar simulations at 82°C, determined the change in Ptrans with temperature for all 2,000 conformations, and observed Hammond behavior directly using Ptrans correlation. The polymer temperature increase only slightly perturbed the transition probabilities. We propose that diffusion along Ptrans may provide the configurational diffusion rate at the top of the barrier. Specifically, given a transition state conformation x0 with estimated Ptrans = 0.5, we selected a large set of subsequent conformations from independent trajectories, each exactly a small time δt after x0 (250ps). Then we calculated Ptrans for each of the new trial conformations. The P(Ptrans|δt=250ps) distribution reflects diffusion along an ideal kinetic reaction coordinate. This approach provides a novel perspective on the nature of a protein folding transition, and provides a framework for quantitative study of activated relaxation kinetics.