Folding and stability of the three-stranded -sheet peptide Betanova: Insights from molecular dynamics simulations

FULL TEXT

Giorgio Colombo 1 2, Danilo Roccatano 1 3, Alan E. Mark 1 *

1Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Biophysical Chemistry, University of Groningen, Nijenborgh, The Netherlands
2Istituto di Biocatalisi e Riconoscimento Molecolare, CNR via Mario Bianco, Milano, Italy
3Department of Chemistry, University of Rome La Sapienza Rome, Italy
email: Alan E. Mark (mark@chem.rug.nl)

*Correspondence to Alan E. Mark, Groningen Biomolecular Science's and Biotechnology, Department of Biophysical Chemistry, University of
Groningen, Nijenborah 4, 9747 AG Groningen, The Netherlands

Keywords

protein folding; molecular dynamics; -sheet; peptide conformation in water; Betanova

Abstract

The dynamics of the three-stranded -sheet peptide Betanova has been studied at four different temperatures (280, 300, 350, and 450 K by molecular dynamics simulation techniques, in explicit water. Two 20-ns simulations at 280 K indicate that the peptide remains very flexible under folding conditions sampling a range of conformations that together satisfy the nuclear magnetic resonance (NMR)-derived experimental constraints. Two simulations at 300 K (above the experimental folding temperature) of 20 ns each show partial formation of native-like structure, which also satisfies most of the NOE constraints at 280 K. At higher temperature, the presence of compact states, in which a series of hydrophobic contacts remain present, are observed. This is consistent with experimental observations regarding the role of hydrophobic contacts in determining the peptide's stability and in initiating the formation of turns and loops. A set of different structures is shown to satisfy NMR-derived distance restraints and a possible mechanism for the folding of the peptide into the NMR-determined structure is proposed.