Characterization of the conformational space of a triple-stranded beta-sheet forming peptide with molecular dynamics simulations

Molecular dynamics (MD) simulations have been performed on a series of
mutants of the 20 amino acid peptide Betanova in order to critically
assess the ability of MD simulations to reproduce the folding and
stability of small beta-sheet-forming peptides on currently accessible
timescales. Simulations were performed in both water and in 40\%
methanol solution, using an explicit solvent model. The simulations
suggest that all mutants adopt a wide range of conformations in
solution, that the structures are highly flexible, and that
stabilization of compact structures is due to a delicate balance of
hydrophobic and polar side-chain interactions. Simulations longer than
100 ns, although not sufficient for a complete thermodynamic and kinetic
description of the system, sample an ensemble of compact conformations
characterized by the loss of ordered beta-sheet secondary structure.
This suggests that no significant free energy barrier separates the
different conformations available. (C) 2004 Wiley-Liss, Inc.