title: Comparative molecular dynamics simulations of the antimicrobial peptide CM15 in model lipid bilayers.
abstract: We report altogether 3-μs molecular dynamics (MD) simulations of the antimicrobial peptide CM15 to systematically investigate its interaction with two model lipid bilayers, pure POPC and mixed POPG:POPC (1:2). Starting with either an α-helical or a random-coil conformation, CM15 is found to insert into both bilayers. Peptide-lipid interaction is stronger with the anionic POPG:POPC than the zwitterionic POPC, which is largely attributed to the electrostatic attraction between CM15 and the negatively charged POPG. Simulations initiated with CM15 as a random coil allowed us to study peptide folding at the lipid-water interface. Interestingly, CM15 folding appears to be faster in POPC than POPG:POPC, which may be explained by a lower activation energy barrier of structural rearrangement in the former system. Our data also suggest that compared with the random-coil conformation, CM15 in a pre-folded α-helix has significantly reduced interactions with the lipids, indicating that peptide initial structures may bias the simulation results considerably on the 100-ns timescale. The implications of this result should be considered when preparing and interpreting future AMP simulations.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA. yiwang@ucsd.edu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Diana E
authors.initials: DE
authors.lastname: Schlamadinger
authors.forename: Judy E
authors.initials: JE
authors.lastname: Kim
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C513873:antimicrobial hybrid peptide CM15; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine