Speed limit of protein folding evidenced in secondary structure dynamics
As the simplest and most prevalent motif of protein folding, α-helix initiation is the starting point of macromolecular complexity. In this work, helix initiation was directly measured via ultrafast temperature-jump spectroscopy on the smallest possible helix nucleus for which only the first turn is formed. The rate's dependence on sequence, length, and temperature reveals the fastest possible events in protein folding dynamics, and it was possible to separate the rate-limiting torsional (conformational) diffusion from the fast annealing of the helix. An analytic coarse-grained model for this process, which predicts the initiation rate as a function of temperature, confirms this picture. Moreover, the stipulations of the model were verified by ensemble-converging all-atom molecular dynamics simulations, which reproduced both the picosecond annealing and the nanosecond diffusion processes observed experimentally.
Additional Information© 2011 National Academy of Sciences. Contributed by Ahmed H. Zewail, August 22, 2011 (sent for review August 4, 2011). Author contributions: M.M.L., O.F.M., G.S.J., and A.H.Z. performed research and wrote the paper. The authors declare no conflict of interest.
Published - Lin2011p16074P_Natl_Acad_Sci_Usa.pdf