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Folding and stability of the three‐stranded β‐sheet peptide Betanova: Insights from molecular dynamics simulations
Author(s) -
Colombo Giorgio,
Roccatano Danilo,
Mark Alan E.
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1175
Subject(s) - folding (dsp implementation) , molecular dynamics , peptide , chemistry , chemical physics , beta sheet , protein folding , nuclear magnetic resonance spectroscopy , stability (learning theory) , resonance (particle physics) , dynamics (music) , crystallography , structural stability , biological system , computational chemistry , physics , stereochemistry , atomic physics , computer science , biochemistry , machine learning , electrical engineering , engineering , structural engineering , acoustics , biology
The dynamics of the three‐stranded β‐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. Proteins 2002;46:380–392. © 2002 Wiley‐Liss, Inc.