Molecular dynamics simulations of beta-hairpin folding

Molecular dynamics simulations of beta-hairpin folding have been carried ou t with a solvent-referenced potential at 274 K. The model peptide V(4)(D)PG V(4) formed stable beta-hairpin conformations and the beta-hairpin ratio ca lculated by the DSSP algorithm was about 56% in the 50-ns simulation. Foldi ng into beta-hairpin conformations is independent of the initial conformati ons. The simulations provided insights into the folding mechanism. The hydr ogen bond often formed in a beta-turn first, and then propagated by forming more hydrogen bonds along the strands. Unfolding and refolding occurred re peatedly during the simulations. Both the hydrogen bonding and the hydropho bic interaction played important roles in forming the ordered structure. Wi thout the hydrophobic effect, stable beta-hairpin conformations did not for m in the simulations. With the same energy functions, the alanine-based pep tide (AAQAA)(3)Y folded into helical conformations, in agreement with exper iments. Folding into an alpha-helix or a beta-hairpin is amino acid sequenc e-dependent. Proteins 1999;37:325-333. (C) 1999 Wiley-Liss, Inc.