Figure 3 |. Comparison of prospective screens against the cryoEM and AF2 structures of the 5-HT2A receptor.

a. The same set of 1.6 billion molecules from ZINC22 were docked against the cryoEM and AF2 structures of the 5-HT2A receptor. 223 molecules were prioritized from the cryoEM docking campaign (left) and 161 from the AF2 docking campaign (right). b. Displacement of the radioligand [³H]-LSD by each molecule at 10 μM (mean ± s.e.m. of three independent replicates). Dashed lines indicate 50% and 90% radioligand displacement respectively. c. The Ca²⁺ mobilization functional assay in agonist mode. Each compound was tested at a concentration of 3 μM. A dashed line indicates agonism equivalent to 10% 5-HT activity. Data are presented as mean ± s.e.m. from three biological replicates. d. The Ca²⁺ mobilization functional assay in antagonist mode. Each compound was tested at a concentration of 3 μM. A dashed line indicates antagonism equivalent to 20% clozapine activity. Data are presented as mean ± s.e.m. from three biological replicates.