Seven A 2A receptor crystal structures were selected to represent different possible protein conformations and associated complementary chemistry, six of which are StaRs 53 published in previous work. These included 3REY co-crystallised with XAC , 4IEY co-crystallised with ZM241385 , 5OLO cocrystallised with Tozadenant 55 , 5OLH co-crystalised with Vipadenant 55 , 5OLV co-crystallised with LUAA47070 , 6GT3 co-crystallised with HTL1071/AZD4635 , and 6ZDR co-crystallised with Chromone . For each structure, missing side chain atoms were added, and ionisable residues were set to their most probable protonation state at pH 7.4, and histidine residues in the binding site based on visual inspection. His250 was protonated in the Nε position, His278 was protonated in both Nδ and Nε positions and based on interactions with Glu169 ECL2 resulting from the conformation of ECL3, His264 ECL3 was either doubly protonated (4EIY 54 , 5OLH , 5OLV , 6GT3 56 , 6ZDR ) or protonated in the Nδ position (3REY 38 , 5OLO ). Compounds to dock were prepared using Moka followed by Corina . Tautomeric and protomeric states with an abundance of at least 20% at pH 7.4 were enumerated with TauThor 60 and Blabber 59 , respectively. Docking was performed using Glide SP .