Before docking, ligands were prepared using Schrodinger LigPrep [80] to enumerate unspecified stereocentres, tautomers and protonation states, with up to 8 variants generated per molecule, based on a pH range of 7±1. Variants were then docked using Glide-SP with default settings, except for OX1R where docked poses were only accepted if they satisfied four out of five grid constraints. The lowest (i.e., best) docking score achieved by any molecule variant was returned as the final docking score. Docking score was normalized between the values of 0 and 1 based on all previously observed docking scores.