A thermodynamic approach to alamethicin pore formation
Asif Rahaman1, Themis Lazaridis
1Department of Chemistry, City College of New York, 160 Convent Avenue, New York, NY 10031, USA.
Biochimica Et Biophysica Acta
|September 28, 2013
Summary
Molecular dynamics simulations reveal alamethicin Rf30 forms stable transmembrane pores. Larger oligomers form open pores, with hexamers and octamers showing optimal energy, supporting the barrel-stave model.
Area of Science:
- Biophysics
- Computational Biology
- Membrane Protein Structure
Background:
- Alamethicin Rf30 is a peptide antibiotic known to form transmembrane pores.
- Understanding the precise structure and energetics of these pores is crucial for elucidating their function.
Purpose of the Study:
- To investigate the structure and energetics of alamethicin Rf30 oligomers within cylindrical pores.
- To determine the preferred oligomeric states and pore sizes for stable alamethicin pore formation.
Main Methods:
- Molecular dynamics simulations were employed using an implicit membrane model.
- The model incorporated the free energy cost of acyl chain hydrophobic area exposure.
- Simulations covered alamethicin Rf30 monomer to nonamer in pores of 5 to 11Å radius.
Main Results:
- Stable, low-energy pores were identified for specific radius and oligomeric number combinations.
- Trimer and tetramer formed closed 6Å pores, while larger oligomers formed open pores.
- Hexamers in 8Å and octamers in 11Å pores exhibited the lowest energy per monomer.
- Pore shape was a hybrid funnel-hourglass, with N-terminal tilt differing from C-terminal.
- Antiparallel bundles showed lower energy than parallel ones.
- Dry aggregates were energetically more favorable than pore-bound aggregates.
Conclusions:
- Results support the barrel-stave model for alamethicin pore formation.
- Alamethicin pores may represent excited states stabilized by voltage and ion flow.
- Transmembrane voltage influences pore stability but not significantly the oligomer structure.
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