The ligands from both datasets were simulated bound to the two BRD4 structural models based on PDBs 2OSS and 4BJX respectively (these are the initial structures used in Aldeghi et al. and Wan et al. ). The former represents the apo BRD4 and the latter the protein bound to a THQ based ligand. The secondary structure of both models is very similar (see Figure ) and the RMSD between the two structures is 0.44 Å. All crystallographic water molecules were retained, including four which are conserved in the binding site of both models. The poses of the ligands in the DIV dataset were extracted from crystal structures (PDBs: 3U5J, 3U5L, 4OGI, 4OGJ, 3MXF, 4MR3, 4MR4, 3SVG, 4J0R and 4HBV), except for one ligand, labelled 11, which was modeled (based on PDB 3SVG) and docked into 2OSS as two conformers. These are the same two conformers used in Aldeghi et al. , differing by a 180 • flip of the trifluorophenyl moiety. The modelled poses were aligned and copied into the 4BJX based models. Poses of the THQ ligands were based on that of I-BET726 as found in the 4BJX structure.