Fig. 7.

GPCR pockets for binding bitopic ligands that target specific ion binding sites. (A) Overview of the pocket positions in 7TM domain. (B) structure of BTL1 receptor with bitopic ligand, PDB: 5X33 (Hori et al., 2018). (C) Model of bitopic ligands designed for binding to KOR Na⁺ allosteric site (Zaidi et al., 2019). (D) Structure of complex with orthosteric ligand and PO4³⁻ ion, PDB: 3RZE (Shimamura et al., 2011). In all panels, semitransparent surface shows orthosteric pocket (orange), allosteric conserved sodium pocket (cyan), and allosteric site in EC loops (green).