The benzoimidazolone is predicted to act as the KAc mimic, with the oxygen atom proposed to form hydrogen bonds with N1039 and, via a structured water molecule, Y993. The benzylic amine is predicted to form a salt bridge with E981, which is the residue that binds to H3R17 contributing to the recognition of the H3 peptide (vide supra). This interaction is likely important for ligand affinity and explains the selectivity of this compound for TRIM33 over TRIM24, as the equivalent residue in TRIM24 is an alanine (A923). This identified a deep cavity in the BRD, a long trench along the interdomain cleft and a small region at the H3K4Me 0 biding site, amongst others. There was no binding site detected in the vicinity of the H3K9Me 3 binding region, consistent with its solvent-exposed nature. Both plausible docking poses, with the benzylic amine oriented 'down' towards the protein surface (Figure ), or 'up' towards the solvent (Figure ), accommodate an interaction of the amine with E981. In the first orientation, the chain of 8 adopts an extended conformation, with the sulfonamide interacting with the side chains of N983 and E984 (Figure ). In the second orientation, the chain twists to interact with one of the structured water molecules and the backbone of I980, N983, and E984 (Figure ). While reasonable, further studies are required to improve our understanding of these proposed binding modes.