Ensembles of low-energy pocket-containing conformations.

<p>(A) To examine the effect of the particular target residues used in generating the ensemble of pocket-containing conformations, we generated separate ensembles from the top-scoring pair of target residues (Ala93 and Arg139, <i>green</i>) and the second-best pair (Ala93 and Ala142, <i>red</i>). We use exemplars to compare the similarity of surface pockets on each conformation, and we show each conformation on the two-dimensional projection that best reflects the pairwise distances between them. The overlap between the two ensembles highlights the robustness of the conformations to the particular target residues. (B) For each member of the Bcl-2 family, we generated an ensemble of conformations from unbiased simulations; the distribution of these energies is shown (<i>black</i>). The range of energies for pocket-containing conformations generated using a biasing potential target residues derived from the Bcl-xL protein interaction site (<i>magenta</i>) or the Mcl-1 protein interaction site (<i>red</i>) suggest that many of these conformations are energetically accessible to these proteins under physiological conditions. All energies shown here were evaluated in the absence of the biasing potential, for fair comparison. Each simulation is started from the structure of the unbound protein; a corresponding figure starting from the peptide-bound structures containing all available complexes is available as <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004081#pcbi.1004081.s005" target="_blank">S5 Fig</a></b>.