City College of New York, Chemistry Department
November 15, 2011
Modeling membrane binding and permeabilization by antimicrobial peptides
Antimicrobial peptides (AMPs) are used by living organisms in all kingdoms of life in their defense against external pathogens. They are thought to act by permeabilizing lipid membranes. Using an implicit membrane model, modified to include pores of different shapes, we have shown that four AMPs (alamethicin, melittin, a magainin analogue, MG-H2, and piscidin 1) bind more strongly to membrane pores, consistent with the idea that they stabilize them. The effective energy of alamethicin in cylindrical pores is similar to that in toroidal pores, whereas that of the other three peptides is lower in toroidal pores. Only alamethicin intercalates into the membrane core; the other three are located exclusively at the hydrophobic/hydrophilic interface. The calculated binding energies of the peptides correlate with their hemolytic activities. We hypothesize that one distinguishing feature of AMPs may be the fact that they are imperfectly amphipathic which allows them to bind more strongly to toroidal pores. An initial test on a melittin-based mutant seems to support this hypothesis. All-atom simulations of alamethicin and melittin in lipid bilayer pores confirm the preference of the former for cylindrical pores and of the latter for toroidal pores.