title: Insertion of peptide chains into lipid membranes: an off-lattice Monte Carlo dynamics model.
abstract: A combination of dynamic Monte Carlo simulation techniques with a hydropathy scale method for the prediction of the location of transmembrane fragments in membrane proteins is described. The new hydropathy scale proposed here is based on experimental data for the interactions of tripeptides with phospholipid membranes (Jacobs, R.E., White, S.H. Biochemistry 26:6127-6134, 1987) and the self-solvation effect in protein systems (Roseman, M.A. J. Mol. Biol. 200:513-522, 1988). The simulations give good predictions both for the state of association and the orientation of the peptide relative to the membrane surface of a number of peptides including Magain2, M2 delta, and melittin. Furthermore, for Pf1 bacteriophage coat protein, in accord with experiment, the simulations predict that the C-terminus forms a transmembrane helix and the N-terminus forms a helix which is adsorbed on the surface of the bilayer. Finally, the present series of simulations provide a number of insights into the mechanism of insertion of peptides into cell membranes.
authors.affiliation: Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: M
authors.initials: M
authors.lastname: Milik
authors.forename: J
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins; D003198:Computer Simulation; D054806:Magainins; D008555:Melitten / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008566:Membranes / Q000737:chemistry*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012995:Solubility; D029867:Xenopus Proteins
chemical_list: D023181:Antimicrobial Cationic Peptides; D036022:Capsid Proteins; D054806:Magainins; D008565:Membrane Proteins; D010455:Peptides; D029867:Xenopus Proteins; C071283:coat protein, Pseudomonas phage Pf1; C053301:magainin 2 peptide, Xenopus; D008555:Melitten