(502b) Interaction of Antimicrobial Peptide Ovispirin with Lipid Bilayers

Antimicrobial peptides kill gram-negative and gram-positive strains of bacteria by interacting with their cell membranes. To understand these interactions at molecular scales it is necessary to develop comprehensive approaches that include novel combinations of experiments and theory. We present one such approach, in which two-dimensional infrared spectroscopy and combined classical-quantum mechanical calculations are used to elucidate the precise nature of interactions between Ovispirin, a 17 residue antimicrobial peptide, and a POPC/POPG mixed bilayer membrane. Classical Monte Carlo and molecular dynamics simulations are used to provide position dependent free-energies for the peptide in the membrane bilayer. A coupled classical-quantum mechanical approach is then used to simulate the 2D IR spectrum corresponding to the classically-generated structures. The results of theoretical predictions are then compared to our own experimental 2D IR measurements. Our results indicate that Ovispirin, in the presence of the membrane, exists in an alpha helical conformation which is adsorbed in an orientation parallel to the bilayer plane. The hydrophobic side chains are buried in the lipid tails, and the polar side chains protrude into the aqueous phase. Our results are consistent with previously published solid-state NMR structures of Ovispirin. Perhaps more importantly, our calculated 2D-IR diagonal line widths for the equilibrium structures obtained in MD our simulations are in quantitative agreement with the corresponding experimental values for the same system.