title: Turn-directed folding dynamics of β-hairpin-forming de novo decapeptide Chignolin.
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.
authors.affiliation: NUS Graduate School for Integrative Sciences & the Singapore-MIT Alliance, National University of Singapore, 4 Engineering Drive 4, Singapore 117576.
authors.forename: Søren
authors.initials: S
authors.lastname: Enemark
authors.forename: Raj
authors.initials: R
authors.lastname: Rajagopalan
mesh_terms: D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D017510:Protein Folding
chemical_list: D009842:Oligopeptides; C506175:chignolin