Fig. 3
From: Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists
MOR structures for pH-specific docking and target area. Overlay of MOR target structures in neutral (blue) and protonated (beige) state. Side chain protonation states at pH 7.4 and 5 were generated according to \(\hbox {p}K_{\hbox {a}}\) values determined by PROPKA, respectively. Side chains in the binding cavity as well as histidine imidazole side chains are depicted. While the imidazole side chains of HIS173 and HIS225 are protonated at acidic pH, they remain neutral in the more buried HIS299 and HIS321. Additionally, the differentially protonated side chain of ASP149 in the binding cavity is shown. The docking target region (“Gridbox”, green lines) was selected based on the fentanyl binding site in the experimental structure (PDB: 8EF5). The left panel shows the MOR from the extracellular angle, and the right panel from the side (90 degrees rotated)