title: β-hairpin forms by rolling up from C-terminal: topological guidance of early folding dynamics.
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.
authors.affiliation: Singapore-MIT Alliance, National University of Singapore, 4 Engineering Drive 3, E4-14-10, Singapore 117576.
authors.forename: Søren
authors.initials: S
authors.lastname: Enemark
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kurniawan
authors.forename: Raj
authors.initials: R
authors.lastname: Rajagopalan
mesh_terms: D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D009842:Oligopeptides; C506175:chignolin