Energy landscape of a β-hairpin peptide in explicit water studied by multicanonical molecular dynamics

A β-hairpin peptide [Ace–Ile–Thr–Val–Asn–Gly–Lys–Thr–Tyr–Nme] in explicit water was studied with multicanonical molecular dynamics simulation. The obtained energy landscape was separated into two regions: deep energy wells and rugged surface. The deep wells consisted of β-hairpin conformations with different hydrogen-bonding patterns, and the rugged surface had random-coils. Both the random-coil and the β-hairpins were stable at 300 K. A mechanism was proposed for the β-hairpin formation: non-oriented thermal fluctuation drives the peptide from the random-coil to a β-hairpin, where the β-turn is formed but the strand is partially disordered. This β-hairpin can switch to a different β-hairpin, where the strand is ordered but the β-turn is disordered.