title: A combined pulse EPR and Monte Carlo simulation study provides molecular insight on peptide-membrane interactions.
abstract: We present a new approach to obtain details on the distribution and average structure and locations of membrane-associated peptides. The approach combines (i) pulse double electron-electron resonance (DEER) to determine intramolecular distances between residues in spin labeled peptides, (ii) electron spin echo envelope modulation (ESEEM) experiments to measure water exposure and the direct interaction of spin labeled peptides with deuterium nuclei on the phospholipid molecules, and (iii) Monte Carlo (MC) simulations to derive the peptide-membrane populations, energetics, and average conformation of the native peptide and mutants mimicking the spin labeling. To demonstrate the approach, we investigated the membrane-bound and solution state of the well-known antimicrobial peptide melittin, used as a model system. A good agreement was obtained between the experimental results and the MC simulations regarding the distribution of distances between the labeled amino acids, the side chain mobility, and the peptide's orientation. A good agreement in the extent of membrane penetration of amino acids in the peptide core was obtained as well, but the EPR data reported a somewhat deeper membrane penetration of the termini compared to the simulations. Overall, melittin adsorbed on the membrane surface, in a monomeric state, as an amphipatic helix with its hydrophobic residues in the hydrocarbon region of the membrane and its charged and polar residues in the lipid headgroup region.
authors.affiliation: Department of Chemical Physics, The Weizmann Institute of Science, Rehovot, Israel 76100.
authors.forename: Michal
authors.initials: M
authors.lastname: Gordon-Grossman
authors.forename: Yana
authors.initials: Y
authors.lastname: Gofman
authors.forename: Herbert
authors.initials: H
authors.lastname: Zimmermann
authors.forename: Veronica
authors.initials: V
authors.lastname: Frydman
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Tal
authors.forename: Daniella
authors.initials: D
authors.lastname: Goldfarb
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D013113:Spin Labels
chemical_list: D008567:Membranes, Artificial; D010455:Peptides; D013113:Spin Labels