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Issue 36, 2012
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Turn-directed folding dynamics of β-hairpin-forming de novo decapeptide Chignolin

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Abstract

Realistic mechanistic pictures of β-hairpin formation, offering valuable insights into some of the key early events in protein folding, are accessible through short designed polypeptides as they allow atomic-level scrutiny through simulations. Here, we present a detailed picture of the dynamics and mechanism of β-hairpin formation of Chignolin, a de novo decapeptide, using extensive, unbiased molecular dynamics simulations. The results provide clear evidence for turn-directed broken-zipper folding and reveal details of turn nucleation and cooperative progression of turn growth, hydrogen-bond formations, and eventual packing of the hydrophobic core. Further, we show that, rather than driving folding through hydrophobic collapse, cross-strand side-chain packing could in fact be rate-limiting as packing frustrations can delay formation of the native hydrophobic core prior to or during folding and even cause relatively long-living misfolded or partially folded states that may nucleate aggregative events in more complex situations. The results support the increasing evidence for turn-centric folding mechanisms for β-hairpin formation suggested recently for GB1 and Peptide 1 based on experiments and simulations but also point to the need for similar examinations of polypeptides with larger numbers of cross-strand hydrophobic residues.

Graphical abstract: Turn-directed folding dynamics of β-hairpin-forming de novo decapeptide Chignolin

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Supplementary files

Article information


Submitted
30 Jan 2012
Accepted
01 Mar 2012
First published
01 Mar 2012

Phys. Chem. Chem. Phys., 2012,14, 12442-12450
Article type
Paper

Turn-directed folding dynamics of β-hairpin-forming de novo decapeptide Chignolin

S. Enemark and R. Rajagopalan, Phys. Chem. Chem. Phys., 2012, 14, 12442
DOI: 10.1039/C2CP40285H

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