title: Multiscale simulations of the antimicrobial peptide maculatin 1.1: water permeation through disordered aggregates.
abstract: The antimicrobial peptide maculatin 1.1 (M1.1) is an amphipathic α-helix that permeabilizes lipid bilayers. In coarse-grained molecular dynamics (CG MD) simulations, M1.1 has previously been shown to form membrane-spanning aggregates in DPPC bilayers. In this study, a simple multiscale methodology has been applied to allow sampling of important regions of the free energy surface at higher resolution. Thus, by back-converting the CG configurations to atomistic representations, it is shown that water is able to permeate through the M1.1 aggregates. Investigation of aggregate stoichiometry shows that at least six peptides are required for water permeation. The aggregates are dynamically disordered structures, and water flux occurs through irregular, fluctuating channels. The results are discussed in relation to experimental data and other simulations of antimicrobial peptides.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Parton
authors.forename: Elena V
authors.initials: EV
authors.lastname: Akhmatskaya
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001001:Anura / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010539:Permeability; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water / Q000378:metabolism*
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; C113499:maculatin-1.1 protein, Litoria; D014867:Water