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Biophysical Journal 72: 627-636 (1997)
© 1997 the Biophysical Society

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Simulation Studies of Alamethicin-Bilayer Interactions

P. C. Biggin *, J. Breed #, H. S. Son * and M. S. P. Sansom *

Laboratory of Molecular Biophysics, University of Oxford, Oxford OX1 3QU, England
Fakultät für Biologie, Universität Konstanz, 78434 Konstanz, Germany

ABSTRACT

Alamethicin is an {alpha}-helical peptide that forms voltage-activated ion channels. Experimental data suggest that channel formation occurs via voltage-dependent insertion of alamethicin helices into lipid bilayers, followed by self-assembly of inserted helices to form a parallel helix bundle. Changes in the kink angle of the alamethicin helix about its central proline residue have also been suggested to play a role in channel gating. Alamethicin helices generated by simulated annealing and restrained molecular dynamics adopt a kink angle similar to that in the x-ray crystal structure, even if such simulations start with an idealized unkinked helix. This suggests that the kinked helix represents a stable conformation of the molecule. Molecular dynamics simulations in the presence of a simple bilayer model and a transbilayer voltage difference are used to explore possible mechanisms of helix insertion. The bilayer is represented by a hydrophobicity potential. An alamethicin helix inserts spontaneously in the absence of a transbilayer voltage. Application of a cis positive voltage decreases the time to insertion. The helix kink angle fluctuates during the simulations. Insertion of the helix is associated with a decrease in the mean kink angle, thus helping the alamethicin molecule to span the bilayer. The simulation results are discussed in terms of models of alamethicin channel gating.






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Copyright © 1997 by the Biophysical Society.