Molecular dynamics investigation of an oriented cyclic peptide nanotube in DMPC bilayers

Abstract

Nanotubes resulting from the self-assembly of cyclic peptides formed by eight α-amino acids and inserted into lipid bilayers have been shown to function as synthetic, integral transmembrane channels. A nanotube consisting of eight cyclo[(L-Trp-D-Leu)3-L-Gln-D-Leu] subunits, organized in an antiparallel, β-sheetlike channel embedded in a hydrated dimyristoylphosphatidylcholine bilayer was investigated in an 8-ns molecular dynamics trajectory. This large-scale statistical simulation brings to light not only the atomic-level structural features of the synthetic channel, but also its dynamical properties. Overall, the nanotube conserves its hollow tubular structure. The calculation reproduces the tilt of the channel with respect to the normal of the bilayer, in reasonable agreement with experiment. The results show a dislocation of the nanotube indicative of a possible disassembly process that may influence the channel conduction. The dynamics of the water in the hollow tubular structure has been characterized, and the conductance of the channel has been estimated. Transport properties of the peptide nanotube are discussed in comparison with other transporters.