Fig. 1.

Generation of pharmacophore queries used for virtual screening. The highest ranked clusters of binding mode solutions with previously characterised PAMs are shown within the α7 nAChR transmembrane domain (A). The Cα trace of TM1-3 helices of the principal subunit and TM2 helix of the complimentary subunit are shown for the open (cyan) and closed (pink) conformations. Also shown are binding mode clusters from which pharmacophore queries were generated for the open (green) and closed (orange) conformations. From the ligands in each cluster, pharmacophore queries were generated for the closed and open conformations (B and C, respectively). Note, only those selected for screening are shown. Features of the pharmacophore are represented as yellow spheres (hydrophobes), green spheres (rings), red hashed spheres (hydrogen bond acceptors) and blue hashed spheres (hydrogen bond donors). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)