Antimicrobial peptides (AMPs) are thought to kill bacteria by permeabilizing their lipid membranes.  We recently used implicit membrane modeling to show that four AMPs bind more strongly to membrane pores than to the flat membrane, consistent with the idea that they stabilize them. In some cases the stronger binding to pores seems to arise from the imperfect amphipathicity of these peptides. One peptide exhibiting striking imperfect amphipathicity is protegrin.  We have found that protegrin requires the positive curvature of toroidal pores to bind to neutral membranes.  Models of protegrin oligomeric beta barrels have been constructed and evaluated energetically.  The NCNC parallel topology was found to be most stable, in apparent disagreement with solid state NMR data.  We have extended this approach to pores in anionic membranes and used it to obtain insights into the lipid selectivity of AMPs.  Ideas emerging from these continuum studies are tested with explicit membrane simulations.

Computational studies of antimicrobial peptides

245th National Meeting (2013)

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