1-Human Defensine Interactions with Model Membranes: Insights from a coarse grain approach

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

SALTO

Congreso; SAB-POSLATAM; 2015

SAB

Defensins are key antimicrobial cationic peptides of the innate immunesystem, the first line of defense against external agents. [1] The goal of thiswork is to get insights at the molecular level of the defensins differentialeffects in model membranes using computer simulations.In order to study the interaction of 1-human defensines (1HD) withmembranes we carried out extensive Molecular Dynamics (MD)simulations 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 ofphospholipids (both zwitterionic and anionic); and glicolipids. In particular,1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline(POPC,zwitterionic lipid) and 2-oleoyl-1-pamlitoyl-sn-glyecro-3-glycerol (POPG,anionic lipid), were used as model of eukaryotic and bacterial cells,respectively. Furthermore, we studied the self-assembly of these two lipidsin the presence of 1HD at different concentrations.The simulations in membranes show that 1HD is essentially found at thelipid-water interphase for both, phospholipids and glicoplipids. However,the interaction is most specific with anionic lipid bilayers. Preliminar self-assembly results show a pore formation. Simulations were also comparedwith fully atomistic (small) membranes.This model was a good tool in order to capture the defensine behavior at themolecular level. This is a first step to the understanding of the differentialeffects of defensines over different probiotic strains [4], aiming thedevelopment of improved probiotic foods.[1] Wu M,Hazlett LD. Cell Tissue 2011. Res 1, 175?188[2] Periole X, Marrink SJ. Methods in molecular biology. 2013. Vol 924, L. Monticelli& E. Salonen Eds., Springer, 2013, pp 533-565.[3] Periole X, Cavalli M, Marrink S, Ceruso, M. Journal of Chemical Theoryand Computation. 2009. 5 (9): 2531?2543[4] Hugo AA, Tymczyszyn EE, Gómez-Zavaglia A, Pérez PF. J Appl Microbiol. 2012Dec;113(6):1491-1497.This work was supported with funds from Agencia Nacional de Promoción Científica yTécnica, CONICET and the University of Buenos Aires.