Ensembles of available pocket shapes contain distinct pocket shapes.

<p>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, <i>all</i> known inhibitors of <i>all</i> 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 <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.s007" target="_blank">S7 Fig</a></b>.