title: Toroidal pores formed by antimicrobial peptides show significant disorder.
abstract: A large variety of antimicrobial peptides have been shown to act, at least in vitro, by poration of the lipid membrane. The nanometre size of these pores, however, complicates their structural characterization by experimental techniques. Here we use molecular dynamics simulations, to study the interaction of a specific class of antimicrobial peptides, melittin, with a dipalmitoylphosphatidylcholine bilayer in atomic detail. We show that transmembrane pores spontaneously form above a critical peptide to lipid ratio. The lipid molecules bend inwards to form a toroidally shaped pore but with only one or two peptides lining the pore. This is in strong contrast to the traditional models of toroidal pores in which the peptides are assumed to adopt a transmembrane orientation. We find that peptide aggregation, either prior or after binding to the membrane surface, is a prerequisite to pore formation. The presence of a stable helical secondary structure of the peptide, however is not. Furthermore, results obtained with modified peptides point to the importance of electrostatic interactions in the poration process. Removing the charges of the basic amino-acid residues of melittin prevents pore formation. It was also found that in the absence of counter ions pores not only form more rapidly but lead to membrane rupture. The rupture process occurs via a novel recursive poration pathway, which we coin the Droste mechanism.
authors.affiliation: Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Durba
authors.initials: D
authors.lastname: Sengupta
authors.forename: Hari
authors.initials: H
authors.lastname: Leontiadou
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mark
authors.forename: Siewert-Jan
authors.initials: SJ
authors.lastname: Marrink
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry*; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry; D008968:Molecular Conformation; D013816:Thermodynamics
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008563:Membrane Lipids; D008555:Melitten; D015060:1,2-Dipalmitoylphosphatidylcholine