This study investigates a combination of BRD4 ligand binding datasets which have been the subjects of earlier studies. The first, previously studied by Aldeghi et al. using a combination of FEP based absolute binding free energy and MMPBSA techniques, contains a diverse set of 11 ligands which will be referred to as the diverse (DIV) dataset. The second was recently studied by our group in collaboration with GlaxoSmithKline 9 (using a combination of ESMACS and ensemble thermodynamic integration approaches) and contains 16 ligands, all based on a single tetrahydroquinoline (THQ) template (consequently we identify this as the THQ dataset). The compounds were selected to represent a range of chemical functionality and binding affinities, despite their shared scaffold. The first 11 compounds are labeled 1 to 9 according to the scheme used by Aldeghi et al. , the THQ based ligands are labeled THQ1 to THQ16 (the numbers correspond to those used in Wan et al. ). The chemical structure of the first 11 compounds and the THQ scaffold are shown in Figure . Details of the groups found at positions R1 to R4 in the THQ based ligands are provided in the Appendices. Ligand 4 was parameterized with a charge of +1. Compounds THQ10 to THQ12 and THQ16 are positively charged (+1), and compounds THQ13 to THQ15 are negatively charged (-1).