Characterization of the conformational space of a triple-stranded β-sheet forming peptide with molecular dynamics simulations

Patricia Soto, Giorgio Colombo

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 β-sheet-forming peptides on currently accessible time-scales. 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 β-sheet secondary structure. This suggests that no significant free energy barrier separates the different conformations available.

Original languageEnglish
Pages (from-to)734-746
Number of pages13
JournalProteins: Structure, Function and Genetics
Volume57
Issue number4
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

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Molecular Dynamics Simulation
Conformations
Molecular dynamics
Peptides
Computer simulation
Thermodynamics
Methanol
Energy barriers
Amino Acids
Free energy
Water
Stabilization
Kinetics

All Science Journal Classification (ASJC) codes

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

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AB - 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 β-sheet-forming peptides on currently accessible time-scales. 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 β-sheet secondary structure. This suggests that no significant free energy barrier separates the different conformations available.

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