(673g) Pore Formation in DOPC/Dopg Bilayers By Antimicrobial Peptide Melittin

Antimicrobial peptides (AMP) kill microbial cells through insertion and damage/permeabilization of the cytoplasmic membranes. Since their mechanism of action differs from that of antibiotics, they could be very useful for combating drug resistant microbes and for treatment of microbial infections. Pore formation in DOPC/DOPG bilayers by antimicrobial peptide melittin was investigated by explicit solvent molecular dynamics (MD) simulation to mimic their permeation action on the cell membrane of microorganism. The effects of number and orientation  of melittin inside the lipid bilayer on the formation of water channel (pore) was characterized. The minimum number of peptides required for pore formation is compared with the critical pore size predicted by a mathematical model based on the free energy of pore formation. The salient features of the simulation results are then compared with experimental data for pore formation as inferred from (i)  leakage of fluorescent dyes (calcein, FD4 and FD20) of different molecular weights encapsulated within liposomes exposed to melittin and (ii)  the antimicrobial activity of melittin against Gram positive bacteria listeria monocytogenes as characterized by absorbance and plate count.