Fig. 1.

Final clusters of docking poses of imipramine in the binding cavity of hSERT. TMs 1 (red), 3 (dark red), 6 (orange), 8 (brown, semitransparent), and 10 (cyan) are depicted in the absence of the remaining TMs for clarity. a, cluster 1 poses contain two distinct placements: the nitrogen atom is placed near Glu493 (a), interaction of the nitrogen with Asp98 is observed (b), and both are analogous to the crystal structure 2Q72. b, cluster 2 poses: Asp98 coordinates the charged nitrogen of imipramine, and the hydrophobic ring system is placed into the hydrophobic region of the binding site. c, cluster 3 poses: the tricyclic ring system is placed in the outer vestibule and the amino propyl side chain reaches into binding site 1. Interactions have been identified using the ligand interactions feature (distance-based) as implemented in MOE.