Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem

Chetna Tyagi, Tamás Marik, C. Vágvölgyi, L. Kredics, F. Ötvös

Research output: Contribution to journalArticle

Abstract

The use of enhanced sampling molecular dynamics simulations to facilitate the folding of proteins is a relatively new approach which has quickly gained momentum in recent years. Accelerated molecular dynamics (aMD) can elucidate the dynamic path from the unfolded state to the near-native state, "flattened" by introducing a non-negative boost to the potential. Alamethicin F30/3 (Alm F30/3), chosen in this study, belongs to the class of peptaibols that are 7-20 residue long, non-ribosomally synthesized, amphipathic molecules that show interesting membrane perturbing activity. The recent studies undertaken on the Alm molecules and their transmembrane channels have been reviewed. Three consecutive simulations of ~900 ns each were carried out where N-terminal folding could be observed within the first 100 ns, while C-terminal folding could only be achieved almost after 800 ns. It took ~1 μs to attain the near-native conformation with stronger potential boost which may take several μs worth of classical MD to produce the same results. The Alm F30/3 hexamer channel was also simulated in an E. coli mimicking membrane under an external electric field that correlates with previous experiments. It can be concluded that aMD simulation techniques are suited to elucidate peptaibol structures and to understand their folding dynamics.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume20
Issue number17
DOIs
Publication statusPublished - Aug 30 2019

Fingerprint

Peptaibols
Alamethicin
Molecular Dynamics Simulation
folding
Molecular dynamics
molecular dynamics
membranes
Membranes
acceleration (physics)
Molecules
Protein Folding
Computer simulation
Escherichia coli
Conformations
simulation
Momentum
Electric fields
Sampling
Proteins
molecules

Keywords

  • accelerated molecular dynamics
  • alamethicin
  • membrane
  • peptaibol

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem. / Tyagi, Chetna; Marik, Tamás; Vágvölgyi, C.; Kredics, L.; Ötvös, F.

In: International journal of molecular sciences, Vol. 20, No. 17, 30.08.2019.

Research output: Contribution to journalArticle

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