β-hairpin forms by rolling up from C-terminal : topological guidance of early folding dynamics

S. Enemark, N.A. Kurniawan, Raj Rajagopalan

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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Abstract

That protein folding is a non-random, guided process has been known even prior to Levinthal's paradox; yet, guided searches, attendant mechanisms and their relation to primary sequence remain obscure. Using extensive molecular dynamics simulations of a β-hairpin with key sequence features similar to those of >13,000 β-hairpins in full proteins, we provide significant insights on the entire pre-folding dynamics at single-residue levels and describe a single, highly coordinated roll-up folding mechanism, with clearly identifiable stages, directing structural progression toward native state. Additional simulations of single-site mutants illustrate the role of three key residues in facilitating this roll-up mechanism. Given the many β-hairpins in full proteins with similar residue arrangements and since β-hairpins are believed to act as nucleation sites in early-stage folding dynamics of full proteins, the topologically guided mechanism seen here may represent one of Nature's strategies for reducing early-stage folding complexity.
Original languageEnglish
Article number649
Pages (from-to)1-6
JournalScientific Reports
Volume2
DOIs
Publication statusPublished - 2012

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