Folding and stability of the three-stranded beta-sheet peptide betanova: Insights from molecular dynamics simulations

The dynamics of the three-stranded beta-sheet peptide Betanova has been
studied at four different temperatures (280, 300, 350, and 450 K by
molecular dynamics simulation techniques, in explicit water. Two 20-ns
simulations at 280 K indicate that the peptide remains very flexible
under ``folding'' conditions sampling a range of conformations that
together satisfy the nuclear magnetic resonance (NMR)-derived
experimental constraints. Two simulations at 300 K (above the
experimental folding, temperature) of 20 ns each show partial formation
of ``native''-like structure, which also satisfies most of the NOE
constraints at 280 K. At higher temperature, the presence of compact
states, in which a series of hydrophobic contacts remain present, are
observed. This is consistent with experimental observations regarding
the role of hydrophobic contacts in determining the peptide's stability
and in initiating the formation of turns and loops. A set of different
structures is shown to satisfy NMR-derived distance restraints and a
possible mechanism for the folding of the peptide into the
NMR-determined structure is proposed. (C) 2002 Wiley-Liss Inc.