Interactiion of antimicrobial peptides with POPC lipid structures modeled by molecular dynamics simulations

BALATTI, GALO EZEQUIEL

Trieste

Exposición; Conference on Atomistic Simulations of Biomolecules: towards a Quantitative Understanding of Life Machinery; 2017

Abdus Salam International Centre for Theoretical Physics

Antimicrobial peptides (AMPs) are key molecules of the innate immune system, the first line of defense against external agents.[1] The goal of our work is to get insights at the molecular level of the AMPs differential effects over model membranes using computer simulations.We started working with human AMPs called defensins, carrying out extensive Molecular Dynamics (MD) simulations mainly through a coarse grain (CG) model. The MARTINI force field[2] was used in combination with the elastic springs network called Elnedyn[3] for defensins. We investigated different model membranes composed of phospholipids (bothzwitterionic and anionic); and glycolipids. In particular, POPC (zwitterionic lipid), and POPG (anionic lipid) were used as a model of eukaryotic and bacterial cells, respectively.Furthermore, we studied the self-assembly of these two lipids in the presence of Human Beta Defensin 1 at different concentrations.The simulations in membranes show that Human Beta Defensin 1 is essentially found at the lipid-water interphase for both, phospholipids and glycoplipids. However, the interaction is most specific with anionic lipid bilayers. Preliminar self-assembly results show a pore formation. Simulations were also compared with fully atomistic (small) membranes.By the other hand we are working also with two peptides obtained from australian tree frogs, called aurein and maculatin. Both peptides show structural features typical of helical AMPs with high lytic activity, the key aspect of AMPs[4]. Nevertheless, is still under discussion themolecular mechanism by which they damage biomembranes.In order to shed light about the molecular mechanism of aurein and maculatin interactions with membranes, we made MARTINI MD simulations, starting from three different configurations: the peptides placed in water near to a POPC planar bilayer, the peptides insidethe hydrophobic core of a POPC planar bilayer, and the molecules randomly distributed along the space. Our results show that both peptides can form pore-like structures, highlighting two different behaviors on the peptide-membrane interactions and membrane leakage of aureinand maculatin, in good agreement with previous experimental observations. 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 membranedestabilization and disintegration.