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

G. E. BALATTI; G. FIDELIO; EE AMBROGGIO; M.F. MARTINI; M. PICKHOLZ

Tucuman

Conferencia; SAB; 2016

sab

Tipo: Póster/OralTópico: Lipid Protein InteractionTítulo: Interaction of antimicrobial peptides with POPC lipid structures modeled by coarse grain molecular dynamics simulationsAutores: Balatti, GE.1, Martini, FM.2 Ambroggio, EE.3, Fidelio, GD.3 and Pickholz, M.1Filiación: 1. Instituto de Nanobiotecnología. (UBA-CONICET)2. Instituto de Química y Metabolismo del Fármaco, (UBA-CONICET)3. Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, (UNC-CONICET). ResumenAntimicrobial Peptides (AMPs) are a wide group of small cationic molecules of the innate immune system. They have proven activity against 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 [1]. Among them, two peptides obtained from australian tree frogs, the aurein 1.2 and the maculatin 1.2 show structural features typical of helical AMPs with high lytic activity, the key aspect of AMPs [ibid]. 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 maculatin interaction with membranes, we carried out extensive Molecular Dynamics (MD) simulations. Taking into account the system size and the time scales required, we have chosen a Coarse Grain approach within the 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 of a POPC planar bilayer (?inside the membrane?), and the molecules randomly distributed along the space (?self-assembly?).Our results show that both peptides can form pore-like structures, highlighting two different behaviors on the peptide-membrane interactions and membrane leakage of aurein and maculatin, in good agreement with previous experimental observations [1]. While maculatin can form a pore maintaining the structure of the bilayer and can induce membrane curvature, aurein exhibits surfactant properties and this may cause the total membrane destabilization and disintegration.1. E.E. Ambroggio, F. Separovic, J.H. Bowie, G.D. Fidelio, L.A. Bagatolli. Biophysical Journal 89 (2005) 1874?1881.2. X. Periole, S.J. Marrink. Methods in molecular biology 925 (2013) 533-565.