Figure 7: AR mechanism of antagonism is disrupted by disease mutations. Many clinical mutations widen the pocket, allowing large antagonist ligands to bind without perturbing H12, ultimately converting antagonists to agonists. A) Wild-type AR with DHT ligand (PDB 1I37) with cavity shown in black. B) T877A mutation (PDB 1I38) introduces the smaller alanine sidechain, increasing cavity volume (yellow) compared to wild-type AR (black). C) W741L mutation widens cavity (yellow) by replacing bulky tryptophan sidechain with leucine.