Fig. 2

Sketch of the differential docking pipeline for the identification of pH-specific MOR ligands. A ligand library was selected and prepared for docking at neutral pH (7.4) and acidic pH (5.0). Target MOR structures (without the G-protein complex) were derived from an experimentally determined structure (Protein Data Bank [22] (PDB): 8EF5 [23]) and side chain protonation states were generated at pH 7.4 and 5 according to \(\hbox {p}K_{\hbox {a}}\) values determined by PROPKA. Docking studies were performed with ligands prepared at pH 7.4 to the neutral MOR (conformation of the experimental structure) and ligands at pH 5.0 to the protonated MOR (conformation after simulation in an acidic environment)