Top: Drug binding site of the closed nucleotide-free model. Tube representation of the transmembrane region of the closed nucleotide-free model. The residues experimentally identified to alter drug specificity are represented in balls and sticks: H61, G64, L65, Y118, V125, M197, T199, S222, I306, A311, V331, T333, F335, S337, V338, L339, I340, G341, A342, F343, Q725, F728, A729, S766, T769, I840, A841, N842, I864, I867, I868, A871, G872, A935, F938, F942, S943, T945, Q946, Y950, F951, S952, Y953, F957, L975, F978, V981, V982, F983, G984 and A985. The two red lines indicate the position of the lipid polar heads in the cellular membrane. Bottom: One predicted position for each docked ligand. Ligands are depicted in purple and the residues experimentally identified to alter their specificity are colored according to their chemical type (carbon in cyan; oxygen in red; nitrogen in blue). (a) colchicine, (b) rhodamineB, (c) verapamil and (d) vinblastine.