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 transiti on pathways, each connecting one random coil configuration with an ideal al pha-helical configuration, were computed and analyzed. The transition pathw ay energetics and mechanism were analyzed in terms of the progression of th e peptide nonbonded contact formation, helicity, end-to-end distance and en ergetics. It was found that (1) localized turns characterized by i, i + 3 h ydrogen 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 app ear to be a necessary step in the transition from coil to helix. These conc lusions are in agreement with the results of more computationally intensive direct molecular dynamics simulations. (C) 1999 Wiley-Liss,Inc.