Figure 2.

Biophysical and structural validation of fragment hits. (A) Docking pose of BAZ2B PHD and Fr3 showing a set of residues shifted in HSQC and clustered at the histone pocket. Residues are colored according to the intensity of the shifts: strong shifts in red (Δδ > + 2σ), intermediate shifts in orange (Δδ > + σ) and lower shifts or no shifts in green (Figure S3). (B) Docking pose of BAZ2B PHD and Fr7 with shifts clustered at the back pocket of BAZ2B and close-up view of in silico predicted interactions. (C) Crystal structure of BAZ2A PHD in complex with Fr19 (in sticks, with green carbons). F_o – F_c electron density map is contoured at 3 σ around the bound fragment. The Thr3 methyl hydrophobic pocket is colored in yellow, and the acidic wall is red. (D) Chemical structures of optimized fragments.