ALAMETHICIN CHANNELS - MODELING VIA RESTRAINED MOLECULAR-DYNAMICS SIMULATIONS

Alamethicin channels have been modelled as approximately parallel bund les of transbilayer helices containing between N = 4 and 8 helices per bundle. Initial models were generated by in vacuo restrained molecula r dynamics (MD) simulations, and were refined by 60 ps MD simulations with water molecules present within and at the mouths of the central p ore. The helix bundles were stabilized by networks of II-bonds between intra-pore water molecules and Gln-7 side-chains. Channel conductance s were predicted on the basis of pore radius profiles, and suggested t hat the N = 4 bundle formed an occluded pore, whereas pores with N gre ater than or equal to 5 helices per bundle were open. Continuum electr ostatics calculations suggested that the N=6 pore is cation-selective, whereas pores with N greater than or equal to 7 helices per bundle we re predicted to be somewhat less ion-selective.