title: Study of orientation and penetration of LAH4 into lipid bilayer membranes: pH and composition dependence.
abstract: LAH4 is an antimicrobial peptide that is believed to possess both antibiotic and DNA delivery capabilities. It is one of a number of membrane-active peptides that show increased affinity toward anionic lipids. Herein, we have performed molecular dynamics simulations to compare LAH4 effects on anionic palmitoyl-oleoyl-phosphatidylglycerol bilayer, which approximate a prokaryotic membrane environment and zwitterionic palmitoyl-oleoyl-phosphatidylcholine bilayer, which approximate a eukaryotic membrane environment. One particular interest in this work is to study how different kinds of lipid bilayers respond to the attraction of LAH4. Remarkably, our data have shown that the depth of peptide penetration strongly depends on membrane composition and pH. At acidic pH, LAH4 has exhibited a high tendency to interact strongly with and be adsorbed on anionic membrane. We have also shown that electrostatic interactions between His11 and the phosphor atoms of bilayers should have a significant impact on the penetration of LAH4. These results provide insights into the interactions of LAH4 and lipid bilayers at the atomic level, which is useful to understand cell selectivity and mechanism of the peptide action.
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Science, Azarbaijan Shahid Madani University, Tabriz, 53714-161, Iran.
authors.forename: Matin
authors.initials: M
authors.lastname: Islami
authors.forename: Faramarz
authors.initials: F
authors.lastname: Mehrnejad
authors.forename: Farahnoosh
authors.initials: F
authors.lastname: Doustdar
authors.forename: Masumeh
authors.initials: M
authors.lastname: Alimohammadi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Khadem-Maaref
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mir-Derikvand
authors.forename: Majid
authors.initials: M
authors.lastname: Taghdir
mesh_terms: D023181:Antimicrobial Cationic Peptides; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; C122154:LAH(4) protein, synthetic; D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: anticancer drugs; antimicrobial peptides; electrostatics interactions; membrane; molecular dynamics simulation