Supramolecular structure of magainin pore as seen by molecular dynamics simulation
Magainins are a group of short cationic peptides isolated from the skin of the African clawed frog Xenopus Leavis. Showing both a broad antibacterial and anticancer activity, they were found to be not hemolytic. Recently, on the basis of the in-plane neutron scattering data, a toroidal model of magainin pores has been proposed. According to this model, strong curvature of membrane is induced which is accompanied by rearrangement of peptide molecules leading to formation of a supramolecular pore. Being strongly associated with lipid head groups, transmembrane alpha-helices of magainins relieve the stress exerted on the membrane by its deformation. We performed numerous molecular dynamics (MD) simulations of magainin-2 amide (M2a) in the lipid membrane environment. The M2a/lipid arrangements included the toroidal pore in a fully hydrated lipid bilayer built of 138 1-palmitoyl 2-oleoyl sn-glycerol-3 phosphatidylethanolamine (POPE) and 46 1-palmitoyl 2-oleoyl sn-glycerol-3 phosphatidyl-rac-glycerol (POPG) molecules as well as two carpet models where helical peptide molecules are bound to the membrane surface. The lipid composition of the model bilayers reflects the most common feature of bacterial membranes, e.g. the presence of negatively charged (POPG) and neutral (POPE) lipids, which for all the huge diversity in lipid make-up of bacterial membranes, are considered to be their main constituents. In the course of MD simulation, a total time of several tens of nanoseconds was covered, allowing us to examine in detail the intricate structure of the lipid/peptide complex and describe quantitatively the influence of strong curvature of membrane on its overall properties in terms of experimentally measurable parameters.