Abstract
The structure of transmembrane pores formed by antimicrobial and cell-penetrating peptides depends on the properties of the membrane and the peptide. To examine the effect of lipid composition, we simulated magainin 2 (MAG2) antiparallel tetramers in DMPC, DMPG and DMPC/PG 1:1 bilayers. Together with the results from our previous work (1), we observe that the MAG2 pore size initially decreases as the anionic content of the membrane increases. However, in pure DMPG the observed pore is similar in size to that in DMPC, but with considerably more unfolded peptides. We also simulated a PGLa parallel tetramer in POPE/PG 3:1 and observed that 1-2 monomers either adopt or tend to adopt a surface orientation during the 5 μs of the simulation, in partial agreement with NMR data (2).We explored the effect of molecularity by simulations of hexamers and octamers of melittin and octamers of MAG2 and comparison with previous tetramer results (1,3). The results show a stable wide pore for the MAG2 octamer, with all the monomers involved in the formation and support of the water channel. On the contrary, in both melittin oligomers the number of peptides in contact with the pore is reduced during the simulation. Finally, we explored the effect of peptide charge by comparing simulations of hexamers of melittin (charge +5) and its gain-of-function variant MELP5 (charge +2) (4). Whereas the melittin hexamer broke up into two trimers, one surrounding a pore and one dry, the MELP5 hexamer simulation resulted in a stable wide pore.(1) Pino-Angeles A, Leveritt JM 3rd and Lazaridis T. PloS Comput Biol (2016) 12(1):e1004570(2) Stranberg E, Zerweck J et al. Biophys J (2013) 104(6):L9-11(3) Leveritt JM 3rd, Pino-Angeles A and Lazaridis T. Biophys J (2015) 108(10):2424-6(4) Wiedman G, Fuselier T et al. J Am Chem Soc (2014) 136(12):4724-31
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