Direct computation of long time processes in peptides and proteins: Reaction path study of the coil-to-helix transition in polyalanine

The MaxFlux reaction path algorithm was used to isolate optimal transition pathways for the coil-to-helix transition in polyalanine, Eighteen transition pathways, each connecting one random coil configuration with an ideal alpha-helical configuration, were computed and analyzed. The transition pathway energetics and mechanism were analyzed in terms of the progression of the peptide nonbonded contact formation, helicity, end-to-end distance and energetics. It was found that (1) localized turns characterized by i, i + 3 hydrogen bonds form in the early stages of the coil-to-helix transition, (2) the peptide first collapses and then becomes somewhat more extended in the final stage of helix formation, and (3) 3(10)-helix formation does not appear to be a necessary step in the transition from coil to helix. These conclusions are in agreement with the results of more computationally intensive direct molecular dynamics simulations. (C) 1999 Wiley-Liss,Inc.