Molecular Dynamics Studies of PEGylated Antimicrobial Peptides with Lipid Bilayers

Abstract

We performed all-atom molecular dynamics (MD) simulations of polyethylene glycol (PEG)-grafted magainin 2 and tachyplesin I with lipid bilayers. In the simulations of PEGylated magainin 2 and tachyplesin I in water, both peptides are wrapped by PEG chains because of the interaction between oxygens of PEGs and the cationic residues of peptides. The α-helical structure of PEGylated magainin 2 is broken, while β-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 β-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 results qualitatively support that PEGylated magainin 2 and tachyplesin I have the different extents of the membrane-permeabilizing activity on lipid bilayer surface.