In this work, the naturally occurring β-hairpin antimicrobial peptide protegrin-1 (PG-1) is studied by molecular dynamics simulation in all-atom sodium dodecylsulfate and dodecylphosphocholine micelles. These simulations provide a high-resolution picture of the interactions between the peptide and simple models of bacterial and mammalian membranes. Both micelles show significant disruption, as is expected for a peptide that is both active against bacteria and toxic to host cells. There is, however, clear differentiation between the behavior in SDS versus DPC, which suggests different mechanisms of interaction for PG-1 with mammalian and bacterial membranes. Specifically, the equilibrium orientation of the peptide relative to SDS is a mirror image of its position relative to DPC. In both systems, the arginine residues of PG-1 strongly interact with the head groups of the micelles. In DPC, the peptide prefers a location closer to the core of the micelle with Phe12, Val14, and Val16 imbedded in the core and the other side of the hairpin, which includes Leu5 and Tyr7, located closer to the surface of the micelle. In SDS, the peptide prefers a location at the micelle-water interface. The peptide position is reversed, with Leu 5 and Cys6 imbedded furthest in the micelle core and Phe12, Val14, and Val16 on the surface of the micelle. We discuss the implications of these results with respect to activity and toxicity.
- Antimicrobial peptides
- DPC micelle
- Membrane mimics
- Molecular dynamics simulation
- Peptide-membrane interactions
- SDS micelle