One driver for the pose change might be entropic gain via water displacement . Indeed previous modelling efforts suggested the PHIP(2) water network to be relatively unstable compared to other bromodomains, with a positive Gibbs binding free energy . Moreover, "magic methyls" are able to significantly alter binding affinity. Overall, these results indicate that the protein binding site defined by this crystal system is stereoselective for the methyl group oriented in an "up" (R) fashion and located on the same side as the compound's cis-oriented amide group oxygens (Fig. ). To fully resolve stereo-selectivity, pure enantiomer soaking is required. The aim here was to rapidly generate crystallographic information from crude reaction mixtures and thus, experiments with pure enantiomers were beyond the scope of this study.