Interaction of a peptide nanotube with a water-membrane interface.
Inserting peptide nanotubes into lipid bilayers modulates the permeability properties of the cell wall, thus conferring potential bacteriocidal capability. Interaction of a peptide nanotube formed by eight cyclo[RRKWLWLW] subunits with the surface of a hydrated dimyristoylphosphatidylcholine bilayer is investigated using molecular dynamics simulations. The present sequence of alternated D-L-alpha-amino acids has been shown to yield remarkable antibacterial in vitro activity, and the chosen topoisomer corresponds to the optimum amphipathy of the tubular structure, whereby non-polar and charged side chains are segregated by the aqueous interface. The cohesion of the nanotube is ensured by a scaffold of intermolecular hydrogen bonds between adjacent cyclic peptides, supplemented by favorable like-charged contacts of arginine side chains. It is further reinforced by interactions of charged residues with the lipid head groups and of non-polar residues with the lipid acyl chains. The simulation reveals a partial breaking of the synthetic channel accompanying its early insertion into the lipid bilayer. The latter opens new questions about how peptide nanotubes permeate the membrane, in particular whether or not (i) self-assembly precedes partitioning and (ii) translocation occurs with the complete tubular structure.
Chipot
Christophe
C
Equipe de dynamique des assemblages membranaires, UMR CNRS/UHP 7565, Institut nancéien de chimie moléculaire, Université Henri Poincaré, BP 239, 54506 Vandoeuvre-lès-Nancy cedex, France. Christophe.Chipot@edam.uhp-nancy.fr
Tarek
Mounir
M
D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D045333:Nanotubes, Peptide / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water
D008051:Lipid Bilayers; D045333:Nanotubes, Peptide; D014867:Water