title: Characterization of the conformational space of a triple-stranded beta-sheet forming peptide with molecular dynamics simulations.
abstract: Molecular dynamics (MD) simulations have been performed on a series of mutants of the 20 amino acid peptide Betanova in order to critically assess the ability of MD simulations to reproduce the folding and stability of small beta-sheet-forming peptides on currently accessible timescales. Simulations were performed in both water and in 40% methanol solution, using an explicit solvent model. The simulations suggest that all mutants adopt a wide range of conformations in solution, that the structures are highly flexible, and that stabilization of compact structures is due to a delicate balance of hydrophobic and polar side-chain interactions. Simulations longer than 100 ns, although not sufficient for a complete thermodynamic and kinetic description of the system, sample an ensemble of compact conformations characterized by the loss of ordered beta-sheet secondary structure. This suggests that no significant free energy barrier separates the different conformations available.
authors.affiliation: Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands. psoto@chem.ucsb.edu
authors.forename: Patricia
authors.initials: P
authors.lastname: Soto
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000032:analysis / Q000737:chemistry; D013997:Time Factors; D014867:Water
chemical_list: D010455:Peptides; D011506:Proteins; C113273:betanova protein, synthetic; D014867:Water; D000432:Methanol