Antimicrobial peptides mechanisms of membrane lysis and permeation by computer simulations

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

La Haya

Conferencia; 15th European Conference on Computational Biology; 2016

Dutch Techcentre for Life Sciences

Antimicrobial peptides (AMPs) are part of the innate immune system, attaching and inserting to the lipidic membranes of external agents among bacteria, fungi, viruses and eukaryoticparasites and killing the cells through a membrane permeation effect.Nevertheles, their molecular mechanisms are not well-known and three different leakage pathways was proposed: the?barrel-stave?, the ?carpet? or the ?toroidal-pore? models. Among AMPs, two peptides obtained from Australian tree frogs, the Aurein 1.2 and the Maculatin 1.2 are proposed as AMPs withdifferent leakage pathways. Here, we carried out extensive Molecular Dynamics (MD) simulations to study the peptide interactions with lipid structures in order to shed light into thesemechanisms.. We have used a coarse grain (CG) model within the MARTINI force field[1]. Three simulation replicates were performed, looking to the self-assembly of 1000 lipids (2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine, POPC) in the presence of the peptides were performed. Furthermore, we simulate both peptides in a presence of a pre-equilibrated bilayer from twodifferent initial configurations: aqueous phase and inside the bilayer.The simulations results showed two different pathways on the membrane leakage, in good agreement with experimentalobservations.[2] While Maculatin can form a pore maintaining the structure of the bilayer, Aurein causes the total membrane destabilization and disintegration. A better understanding ofAMPs molecular behavior can aim the development of new antimicrobials drugs.[1] X. Periole, S.J. Marrink. Methods in molecular biology 925 (2013) 533-565[2] E.E. Ambroggio et alBiophysical Journal 89 (2005) 1874?1881