A coarse-grained approach to studying the interactions of the antimicrobial peptides aurein 1.2 and maculatin 1.1 with POPG/POPE lipid mixtures

BALATTI, G. E.; MARTINI, M. F.; PICKHOLZ, M.

JOURNAL OF MOLECULAR MODELING - (Print)

SPRINGER

Año: 2018 vol. 24 p. 1 - 9

1610-2940

In the present work we investigated the differential interactions of the antimicrobial peptides (AMPs) aurein 1.2 andmaculatin 1.1 with a bilayer composed of a mixture of the lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glyc-erol) (POPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE). We carried out molecular dynamics(MD) simulations using a coarse-grained approach within the MARTINI force field. The POPE/POPG mixture was used as asimple model of a bacterial (prokaryotic cell) membrane. The results were compared with our previous findings for struc-tures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a representative lipid of mammalian cells. We startedthe simulations of the peptide?lipid system from two different initial conditions: peptides in water and peptides inside thehydrophobic core of the membrane, employing a pre-assembled lipid bilayer in both cases. Our results show similarities anddifferences regarding the molecular behavior of the peptides in POPE/POPG in comparison to their behavior in a POPCmembrane. For instance, aurein 1.2 molecules can adopt similar pore-like structures on both POPG/POPE and POPCmembranes, but the peptides are found deeper in the hydrophobic core in the former. Maculatin 1.1 molecules, in turn,achieve very similar structures in both kinds of bilayers: they have a strong tendency to form clusters and induce curvature.Therefore, the results of this study provide insight into the mechanisms of action of these two peptides in membrane leakage,which allows organisms to protect themselves against potentially harmful bacteria.