Table 4.
ToxCast active enrichment from allosteric pockets, and the consensus over different pockets
| Receptor | logAUC (EF1) from OBP | logAUC (EF1) from ABP1 | Consensus1 logAUC (EF1) | ToxCast actives% favoring ABP1 | logAUC (EF1) from ABP2 | Consensus2 logAUC (EF1) | ToxCast actives% favoring ABP2 |
|---|---|---|---|---|---|---|---|
| AR* | 35.3 (9.4) | 22.4 (1.0) | 31.4 (10.8) | 7.0 | 16.2 (1.0) | 31.3 (10.8) | 6.1 |
| GR | 29.3 (7.6) | 27.0 (5.3) | 32.6 (7.6) | 19.0 | 15.4 (2.4) | 32.4 (7.6) | 5.4 |
| PR | 31.1 (15.8) | 27.1 (10.5) | 33.1 (17.6) | 12.5 | 19.2 (4.4) | 33.2 (17.6) | 6.2 |
| ERα | 31.7 (12.6) | 23.3 (4.2) | 27.1 (12.6) | 7.5 | 14.5 (2.1) | 27.2 (12.6) | 3.6 |
| ERβ | 28.2 (8.1) | 23.3 (2.8) | 31.0 (9.0) | 12.5 | 14.6 (2.8) | 30.9 (9.0) | 3.6 |
| PPARα | 21.2 (7.9) | 28.5 (5.3) | 32.6 (7.9) | 35.0 | 13.8 (2.7) | 32.4 (7.9) | 4.0 |
| PPARγ | 21.0 (4.6) | 21.0 (2.8) | 22.6 (3.7) | 21.6 | 15.6 (2.8) | 23.2 (3.7) | 3.4 |
| RARα | 25.1 (2.4) | 21.0 (4.8) | 23.6 (3.6) | 11.4 | 14.8 (2.4) | 23.2 (3.6) | 3.8 |
| RORγ# | 22.9 (4.8) | 22.4 (3.6) | 24.2 (3.6) | 12.2 | 16.1 (1.2) | 24.0 (3.6) | 4.8 |
| VDR | 21.3 (1.8) | 19.4 (2.4) | 21.7 (1.8) | 4.2 | 16.9 (1.1) | 21.8 (1.8) | 3.4 |
| RXRα | 20.7 (4.6) | 22.2 (4.6) | 25.1 (4.6) | 16.8 | 15.0 (2.3) | 21.2 (4.6) | 4.5 |
| LXRβ | 19.0 (2.1) | 14.8 (0.0) | 19.0 (2.1) | 1.0 | 15.4 (2.1) | 19.0 (2.1) | 1.0 |
logAUC(EF1) from OBP, logAUC (EF1) from the orthosteric binding pocket in the structure of the best resolution. Consensus1 logAUC/EF1, Consensus logAUC/EF1 from OBP and ABP1. Consensus2 logAUC/EF1, Consensus logAUC/EF1 from OBP, ABP1, and ABP2. ToxCast actives% favoring ABP1, the percentage of ToxCAST actives that were scored better by ABP1 than OBP. Consensus1 logAUC/EF1 or Consensus2 logAUC/EF1 are highlighted in bold or italic fonts when they are > 10% better or worse than logAUC (EF1) from OBP
*For AR, the reported alternative binding pocket (ABP1) (PDB ID: 2PIW) was used for docking, the ABP1 in each of the other 11 NRs was derived by superposing the best resolution structure onto 2PIW
#For RORγ, the reported alternative binding pocket (ABP2) (PDB ID: 5C4T) was used for docking, the ABP2 in each of the other 11 NRs was derived by superposing the best resolution structure onto 5C4T
Consensus1 logAUC/EF1 or Consensus2 logAUC/EF1 are highlighted in bold or italic fonts when they are >10% better or worse than logAUC (EF1) from OBP