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

BALATTI, GALO EZEQUIEL; MARTINI, MARIA FLORENCIA; PICKHOLZ, MONICA ANDREA

Salto

Congreso; Latin American Crosstalk in Biophysics and Physiology.; 2015

Sociedad Uruguaya de Biociencias (SBF.uy-SUB) / LATIN AMERICAN FEDERATION OF BIOPHYSICAL SOCIETIES

Defensins are key antimicrobial cationic peptides of the innate immunesystem, the first line of defense against external agents. [1] The goal of this work is to get insights at the molecular level of the defensins differential effects 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 of phospholipids (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 lipids in 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 the molecular level. This is a first step to the understanding of the differential effects of defensines over different probiotic strains [4], aiming the development 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 Theory and Computation. 2009. 5 (9): 2531?2543[4] Hugo AA, Tymczyszyn EE, Gómez-Zavaglia A, Pérez PF. J Appl Microbiol. 2012 Dec;113(6):1491-1497.