MOLECULAR MODELING OF STAPHYLOCOCCAL DELTA-TOXIN ION CHANNELS BY RESTRAINED MOLECULAR-DYNAMICS

delta-Toxin is a 26-residue channel-forming peptide from Staphylococcu s aureus which forms an amphipathic alpha-helix in a membrane environm ent, Channel formation in planar bilayers suggests that an average of six delta-toxin helices self-assemble to form transbilayer pores. Mole cular models for channels formed by delta-toxin and by a synthetic ana logue have been generated using a simulated annealing protocol applied via restrained molecular dynamics. These models are analysed in terms of the predicted geometric and energetic properties of the transbilay er pores, Pore radius calculations of the models demonstrate that ring s of channel-lining residues contribute a series of constrictions alon g the pore. Electrostatic properties of the pores are determined both by pore-lining charged side chains and by the aligned helix dipoles of the parallel helix bundle. Molecular dynamics simulations (100 ps) of delta-toxin models containing intra-pore water were performed. Analys is of the resultant dynamics trajectories further supports the proposa l that alternative conformations of pore-constricting side chains may be responsible for the observed conductance heterogeneity of delta-tox in ion channels.