Surface binding of alamethicin stabilizes its helical structure: Moleculardynamics simulations

Alamethicin is an amphipathic alpha-helical peptide that forms ion channels . An early event in channel formation is believed to be the binding of alam ethicin to the surface of a lipid bilayer, Molecular dynamics simulations a re used to compare the structural and dynamic properties of alamethicin in water and alamethicin bound to the surface of a phosphatidylcholine bilayer . The bilayer surface simulation corresponded to a loosely bound alamethici n molecule that interacted with lipid headgroups but did not penetrate the hydrophobic core of the bilayer. Both simulations started with the peptide molecule in an alpha-helical conformation and lasted 2 ns. In water, the he lix started to unfold after similar to 300 ps and by the end of the simulat ion only the N-terminal region of the peptide remained alpha-helical and th e molecule had collapsed into a more compact form. At the surface of the bi layer, loss of helicity was restricted to the C-terminal third of the molec ule and the rod-shaped structure of the peptide was retained. In the surfac e simulation about 10% of the peptide/water H-bonds were replaced by peptid e/lipid H-bonds. These simulations suggest that some degree of stabilizatio n of an amphipathic alpha-helix occurs at a bilayer surface even without in teractions between hydrophobic side chains and the acyl chain core of the b ilayer.