Selectivity by Small-Molecule Inhibitors of Protein Interactions Can Be Driven by Protein Surface Fluctuations
Fig 6
Ensembles of available pocket shapes contain distinct pocket shapes.
We define the “distinctness” of a pocket as the difference in exemplar distances of the closest conformation from a different family member, and the closest conformation from one’s own ensemble. Histograms are shown over conformations that comprise the ensembles used above. By this measure, all known inhibitors of all Bcl-2 family members bind to pockets that are not unique to their cognate target protein (i.e. low “distinctness”). Data are shown for three representative Bcl-2 family members, the complete set are included as S7 Fig.