Folding and Unfolding of Two Mixed α/β Peptides

We present a molecular dynamics simulation study of two peptides containing alpha- and beta-amino acid residues. According to experiment, the two peptides differ in the dominant fold when solvated in methanol: one shows a helical fold, the other a beta hairpin. The simulations at 300 and 340 K were done by starting from a NMR spectroscopic model structure and from an extended (denatured) structure. The typical structural features of the two peptides are reproduced and a folding/unfolding equilibrium is observed on the nanosecond timescale at 300 K. Analysis of proton-proton NOE distance bounds and backbone (3)J coupling constants gives results consistent with the experimental data. We conclude that our simulations are complementary to the experiments by providing detailed information on the conformational disturbutions.