Lactoferricin Peptides Characterized Using All-Atom Molecular Dynamics Simulations and Solid State NMR

Abstract

Lactoferricin B is a cationic antimicrobial peptide with broad spectrum effectiveness. A small hexapeptide (LfB6, RRWQWR-NH2) extracted from this peptide has similar antimicrobial properties that can be enhanced by attaching a short fatty acid to the N-terminus (C6-LfB6). The mechanism for interaction between the antimicrobial peptide and the bacterial cell membrane is not well understood, but it is hypothesized to depend on lipid composition. Bacterial membranes generally contain a significant (20-25%) fraction of negatively charged lipids, in contrast with the zwitterionic mammalian membranes. In the case of LfB6, the presence of the tryptophans and arginines is thought to promote selective interactions with the negatively charged bacterial membranes. Here, we investigate the interactions of both LfB6 and C6-LfB6 with lipid bilayers using all-atom molecular dynamics simulations in concert with solid state 2H NMR. In particular, we investigated the peptide interactions with a model bacterial membrane (3:1 POPE:POPG) and a model mammalian membrane (POPC), and compared our results to solid state 2H NMR data. The results show subtle changes in the membranes and conformational substates of the lipopeptides, elucidating the effects of antimicrobial peptide binding.