Effects of PEGylation on the Binding Interaction of Magainin 2 and Tachyplesin I with Lipid Bilayer Surface

Poly(ethylene glycol) (PEG)-grafted magainin 2 and tachyplesin I were simulated with lipid bilayers. In the simulations of PEGylated magainin 2 and tachyplesin I in water, both peptides are wrapped by PEG chains. The alpha-helical structure of PEGylated magainin 2 is broken in water, while the beta-sheet of PEGylated tachyplesin I keeps stable, similar to the structural behavior of unPEGylated peptides, in agreement with experiments. Simulations of PEGylated peptides with lipid bilayers show that PEG chains block the electrostatic interaction between cationic residues of peptides and anionic phosphates of lipids, leading to the less binding of the peptide to the bilayer surface, which is observed more significantly for magainin 2 than for tachyplesin I. Since the random-coiled magainin 2 can be more completely covered by PEGs than does the beta-sheet tachyplesin I, the PEGylation effect on the decreased binding is larger for magainin 2, showing the dependence of PEGylation on the peptide structure. These simulation findings qualitatively support the experimental observation of the different extents of the reduced membrane-permeabilizing activity for PEGylated magainin 2 and tachyplesin I.