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Abstract

Fifty-five molecular dynamics runs of two three-stranded antiparallel β-sheet peptides were performed to investigate the relative importance of amino acid sequence and native topology. The two peptides consist of 20 residues each and have a sequence identity of 15 %. One peptide has Gly-Ser (GS) at both turns, while the other has d-Pro-Gly ((D)PG). The simulations successfully reproduce the NMR solution conformations, irrespective of the starting structure. The large number of folding events sampled along the trajectories at 360 K (total simulation time of about 5 micros) yield a projection of the free-energy landscape onto two significant progress variables. The two peptides have compact denatured states, similar free-energy surfaces, and folding pathways that involve the formation of a β-hairpin followed by consolidation of the unstructured strand. For the GS peptide, there are 33 folding events that start by the formation of the 2-3 β-hairpin and 17 with first the 1-2 β-hairpin. For the (D)PG peptide, the statistical predominance is opposite, 16 and 47 folding events start from the 2-3 β-hairpin and the 1-2 β-hairpin, respectively. These simulation results indicate that the overall shape of the free-energy surface is defined primarily by the native-state topology, in agreement with an ever-increasing amount of experimental and theoretical evidence, while the amino acid sequence determines the statistically predominant order of the events.

Year of Publication
2001
Journal
Journal of Molecular Biology
Volume
306
Issue
4
Number of Pages
837-850
Date Published
2001 Mar 2
Type of Article
Research Article
ISSN Number
0022-2836
DOI
10.1006/jmbi.2000.4400
Alternate Journal
J. Mol. Biol.
PMID
11243792
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