Themis Lazaridis

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.

Themis Lazaridis obtained a Diploma in Chemical Engineering from the Aristotle University of Thessaloniki, Greece, in 1987.  He then pursued doctoral studies in Chemical Engineering at the University of Delaware.  Upon completion of his PhD thesis in 1992, he joined the group of Martin Karplus in the Harvard Chemistry department and in 1998 the faculty of the Chemistry Department at the City College of New York (CUNY).  His research is in the area of theoretical and computational biophysics, with emphasis on statistical thermodynamics of solvation, protein stability, implicit solvation models, ligand binding, and protein-membrane interactions.  For more information, please visit: http://www.sci.ccny.cuny.edu/~themis/