title: Simulating the mechanism of antimicrobial lipopeptides with all-atom molecular dynamics.
abstract: The emergence of antibiotic resistant pathogens is one of the major medical concerns of the 21st century, prompting renewed interest in the development of novel antimicrobial compounds. Here we use microsecond-scale all-atom molecular dynamics simulations to characterize the structure, dynamics, and membrane-binding mechanism of a synthetic antimicrobial lipopeptide, C16-KGGK. Our simulations suggest that these lipopeptides prefer to aggregate in solution and alter the intrinsic order of the lipid bilayer upon binding. From these results and previous coarse-grained simulations, we have developed a simple model for the binding and insertion process for these lipopeptides.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Horn
authors.forename: Tod D
authors.initials: TD
authors.lastname: Romo
authors.forename: Alan
authors.initials: A
authors.lastname: Grossfield
mesh_terms: D000465:Algorithms; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D055666:Lipopeptides / Q000737:chemistry* / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D008051:Lipid Bilayers; D055666:Lipopeptides; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol