Ensembles of available pocket shapes explain ligand selectivity across the Bcl-2 family.

<p>(A) For each inhibitor-bound pocket, the exemplar distance to the most similar pocket is indicated by color gradient, with all distances expressed as Z-scores (<i>green</i> are most similar, <i>red</i> are most dissimilar; the range of colors for each row is normalized across that row). Markings inside the cells denote experimental reports [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.ref011" target="_blank">11</a>,<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.ref051" target="_blank">51</a>,<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.ref060" target="_blank">60</a>,<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.ref067" target="_blank">67</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.ref076" target="_blank">76</a>] for a given protein-ligand pair (Kd or Ki where available, otherwise IC50): ✔✔✔ indicates < 0.1 μM, ✔✔ indicates 0.1–1 μM, ✔ indicates binding weaker than 1 μM, and ✗ indicates that binding was not detectable/quantifiable. Cells that do not include any markings correspond to protein-ligand pairs for which binding data has not been reported. Numbering corresponds to complexes as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.s010" target="_blank">S1 Table</a>. A representative subset of the complexes are included in this figure; a corresponding figure containing all complexes is available as <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.s008" target="_blank">S8 Fig</a>. The underlying raw data are included in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.s014" target="_blank">S5 Table</a> (exemplar distances) and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.s016" target="_blank">S7 Table</a> (citations to binding data). (B) A receiver operating characteristic (ROC) plot demonstrating the performance of exemplar distances for predicting whether a given compound is active against a particular member of the Bcl-2 protein family.