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Alamethicin channels - modelling via restrained molecular dynamics simulations
J Breed1, P C Biggin, I D Kerr
1Laboratory of Molecular Biophysics, University of Oxford, UK.
Biochimica Et Biophysica Acta
|April 26, 1997
Summary
Alamethicin channels, modeled as helix bundles, show that 5 or more helices create open pores. Ion selectivity varies with helix number, with N=6 being cation-selective.
Area of Science:
- Biophysics
- Computational Biology
- Membrane Protein Structure
Background:
- Alamethicin channels are voltage-gated ion channels formed by amphipathic alpha-helices.
- Previous models proposed varying numbers of helices (N=4-8) in alamethicin channel bundles.
Purpose of the Study:
- To computationally model alamethicin channel structures.
- To investigate the relationship between helix bundle size and channel function (pore opening and ion selectivity).
Main Methods:
- Molecular dynamics (MD) simulations in vacuo and with explicit water.
- Refinement of models using restrained MD simulations.
- Analysis of pore radius profiles and continuum electrostatics calculations.
Main Results:
- Models of alamethicin channels with 4 to 8 helices were successfully generated and refined.
- Pore radius profiles indicated that N=4 bundles form occluded pores, while N>=5 bundles form open pores.
- Continuum electrostatics predicted cation selectivity for N=6 pores and reduced selectivity for N>=7 pores.
Conclusions:
- The number of helices in an alamethicin channel bundle significantly influences its structural and functional properties.
- A minimum of 5 helices is required for pore opening.
- Ion selectivity is dependent on the precise number of helices within the bundle.