Figure 2.

Binding mode of (A) doxepin (1, magenta carbon atoms) in human H₁R (PDB code 3RZE (Shimamura et al., 2011)), (B) (R)-3-quinuclidinylbenzilate (2, green carbon atoms) in human M₂R (PDB code 3UON (Haga et al., 2012)), (C) tiotropium (3, orange carbon atoms) in rat M₃R (PDB code 4DAJ (Kruse et al., 2012)), (D) (S)-carvedilol (4, blue carbon atoms) in turkey β₁AR (PDB code 4AMJ (Warne et al., 2012)), (E) (S)-carazolol (5, red carbon atoms) in human β₂AR (PDB code 2RH1 (Cherezov et al., 2007)) and (F) (S)-eticlopride [(6, brown carbon atoms in D₃R (PDB code 3PBL (Chien et al., 2010)]. The yellow ribbons represent parts of the backbone of transmembrane (TM) helices 2, 3, 5, 6 and 7. Selected binding site residues are depicted as ball-and-sticks with light grey carbon atoms. Oxygen, nitrogen, sulphur, hydrogen and chlorine atoms are coloured red, blue, yellow, cyan and green, respectively. Hydrogen bonds are depicted by black dashes. Polar hydrogen atoms of the ligand are shown, but are omitted for the pocket residues. The labels for W^6.48 are omitted for all structures as well as F^6.52 for H₁R, β₁AR, β₂AR and D₃R for clarity purposes. (G) Molecular interaction fingerprint (IFP) (Marcou and Rognan, 2007) bitstrings describing the binding poses of 1–6 (A–F), encoding different interaction types (negatively charged, positively charged, H-bond acceptor, H-bond donor, aromatic face-to-edge, aromatic-face-to-face and hydrophobic) for each residue in the binding site. For reasons of clarity, only the bit strings of residues D^3.32, 5.42, 5.46, 6.52, 6.55, and 7.39 are shown. All binding modes are presented in a similar fashion throughout the manuscript. 2D structures of the molecules are presented in Figure 3A.