Folding simulations of a three-stranded antiparallel β-sheet peptide

TitleFolding simulations of a three-stranded antiparallel β-sheet peptide
Publication TypeJournal Article
Year of Publication2000
AuthorsFerrara P., Caflisch A.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue20
Pagination10780-10785
Date Published2000 Sep 26
Type of ArticleResearch Article
ISSN0027-8424
KeywordsModels, Molecular, Peptides, Protein Folding
Abstract

Protein folding is a grand challenge of the postgenomic era. In this paper, 58 folding events sampled during 47 molecular dynamics trajectories for a total simulation time of more than 4 μs provide an atomic detail picture of the folding of a 20-residue synthetic peptide with a stable three-stranded antiparallel β-sheet fold. The simulations successfully reproduce the NMR solution conformation, irrespective of the starting structure. The sampling of the conformational space is sufficient to determine the free energy surface and localize the minima and transition states. The statistically predominant folding pathway involves the formation of contacts between strands 2 and 3, starting with the side chains close to the turn, followed by association of the N-terminal strand onto the preformed 2-3 β-hairpin. The folding mechanism presented here, formation of a β-hairpin followed by consolidation, is in agreement with a computational study of the free energy surface of another synthetic three-stranded antiparallel β-sheet by Bursulaya and Brooks [(1999) J. Am. Chem. Soc. 121, 9947-9951]. Hence, it might hold in general for antiparallel β-sheets with short turns.

DOI10.1073/pnas.190324897
pubindex

0027

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID10984515
PubMed Central IDPMC27100
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