Interaction of antimicrobial peptides with POPC lipid structures modeled by coarse-grained molecular dynamics simulations

BALATTI, GALO E.; MARTINI, M. FLORENCIA; AMBROGGIO E.E.,; FIDELIO G.D.,; PICKHOLZ, MÓNICA

San Miguel de Tucumán

Congreso; III LAFEBS, 9 Iberoamerican congress of Biophysics and XLV Annual Meeting of Argentinian Biophysical Society; 2016

SAB

Antimicrobial Peptides (AMPs) are a wide group of small cationicmolecules of the innate immune system. They have proven activityagainst agents among bacteria, fungi, viruses and eukaryotic parasites.It is suggested that they act by binding to the bilayer increasing the permeabilityof the membrane [1].206Poster Lipid-Protein interactionAmong them, two peptides obtained from australian tree frogs, the aurein1.2 and the maculatin 1.2 show structural features typical of helicalAMPs with high lytic activity, the key aspect of AMPs [ibid]. Nevertheless,is still under discussion the molecular mechanism by which theydamage biomembranes.In order to shed light about the molecular mechanism of aurein and maculatininteraction with membranes, we carried out extensive MolecularDynamics (MD) simulations. Taking into account the system size andthe time scales required, we have chosen a coarse grain approach withinthe MARTINI force field [2].The simulations were carried out starting from three different configurations:the peptides placed in water near to a POPC planar bilayer(?outside the membrane?), the peptides inside the hydrophobic core ofa POPC planar bilayer (?inside the membrane?), and the molecules randomlydistributed along the space (?self-assembly?). Our results showthat both peptides can form pore-like structures, highlighting two differentbehaviors on the peptide-membrane interactions and membraneleakage of aurein and maculatin, in good agreement with previous experimentalobservations [1]. While maculatin can form a pore maintainingthe structure of the bilayer and can induce membrane curvature,aurein exhibits surfactant properties and this may cause the total membranedestabilization and disintegration.References1. E.E. Ambroggio, F. Separovic, J.H. Bowie, G.D. Fidelio, L.A. Bagatolli. BiophysicalJournal 89 (2005) 1874?1881.2. X. Periole, S.J. Marrink. Methods in molecular biology 925 (2013) 533-565..