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

BALATTI, GALO EZEQUIEL; MARTINI, MARÍA FLORENCIA; AMBROGGIO, ERNESTO ESTEBAN; PICKHOLZ, MÓNICA ANDREA; FIDELIO, GERARDO DANIEL

San Miguel de Tucumán

Congreso; IX IberoAmerican Congress of Biophysics / XLV Reunión Anual SAB / III Latin American Federation of Biophysical Societies; 2016

Antimicrobial Peptides (AMPs) are a wide group of small cationic molecules 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 permeability of the membrane. Among them, two peptides obtained from australian tree frogs, the au-rein 1.2 and the maculatin 1.2 show structural features typical of helicalAMPs with high lytic activity, the key aspect of AMPs. Nevertheless, is still under discussion the molecular mechanism by which they damage biomembranes.In order to shed light about the molecular mechanism of aurein and mac-ulatin interaction 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.The simulations were carried out starting from three different config-urations: 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 ran-domly distributed along the space (?self-assembly?). Our results showthat both peptides can form pore-like structures, highlighting two dif-ferent behaviors on the peptide-membrane interactions and membraneleakage of aurein and maculatin, in good agreement with previous ex-perimental observations. While maculatin can form a pore main-taining the structure of the bilayer and can induce membrane curvature,aurein exhibits surfactant properties and this may cause the total mem-brane destabilization and disintegration.