Table 3.
Statistical parameters and mutual pharmacophoric features distances (A°) of pharmacophore models developed using most probable binding conformations of selected templates in open and closed state of hERG.
| Compound | hERG open state conformation model | hERG close state conformation model | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Model template | Model distances A° | Model statistics | Model template | Model distances A° | Model statistics | ||||||||||
| 1 | MK-499 |  |
Aro 1 | Hyd | Aro 2 | HBA | TP: 102/177 TN:75/177 FP:7/32 FN:25/32 MCC = 0.70 |
 |
Aro1 | Hyd | Aro.2 | HBA | TP: 108/177 TN:69/177 FP:6/32 FN:24/32 MCC = 0.71 |
||
| Aro1 | 0 | 5.8 | 6.6 | 6.1 | Aro1 | 0 | 5.3 | 6.1 | 5.8 | ||||||
| Hyd | 5.8 | 0 | 7.7 | 6.3 | Hyd | 5.3 | 0 | 4.7 | 6.3 | ||||||
| Aro2 | 6.6 | 7.7 | 0 | 8.2 | Aro2 | 6.1 | 4.7 | 0 | 7.2 | ||||||
| HBA | 6.1 | 6.3 | 8.2 | 0 | HBA | 5.8 | 6.3 | 7.2 | 0 | ||||||
| 2 | E4031 |  |
Aro 1 | Hyd | Aro.2 | HBA | TP: 105/177 TN:72/177 FP:9/32 FN:23/32 MCC = 0.69 |
 |
Aro1 | Hyd | Aro.2 | HBA | TP: 105/177 TN:72/177 FP:9/32 FN:23/32 MCC = 0.69 |
||
| Aro1 | 0 | 7.2 | 5.1 | 8.1 | Aro1 | 0 | 6.3 | 5.4 | 6.8 | ||||||
| Hyd | 7.2 | 0 | 6.2 | 5.6 | Hyd | 6.3 | 0 | 5.7 | 4.3 | ||||||
| Aro2 | 5.1 | 6.2 | 0 | 6.1 | Aro2 | 5.4 | 5.7 | 0 | 5.5 | ||||||
| HBA | 8.1 | 5.6 | 6.1 | 0 | HBA | 6.8 | 4.3 | 5.5 | 0 | ||||||
| 3 | Dofetilide |  |
Aro 1 | Hyd.1 | Aro.2 | HBA | TP:108/177 TN:71/177 FP:8/32 FN:24/32 MCC = 0.69 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:110/177 TN:73/177 FP:6/32 FN:26/32 MCC = 0.70 |
||
| Aro1 | 0 | 6.3 | 6.6 | 7.3 | Aro1 | 0 | 8.2 | 5.1 | 6.6 | ||||||
| Hyd | 6.3 | 0 | 6.4 | 5.2 | Hyd | 8.2 | 0 | 4.6 | 6.8 | ||||||
| Aro2 | 6.6 | 6.4 | 0 | 8.2 | Aro2 | 5.1 | 4.6 | 0 | 6.1 | ||||||
| HBA | 7.3 | 5.2 | 8.2 | 0 | HBA | 6.6 | 6.8 | 6.1 | 0 | ||||||
| 4 | Trimethoprim |  |
Aro 1 | Hyd | Aro.2 | HBA | TP: 99/177 TN:78/177 FP:9/32 FN:23/32 MCC = 0.69 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:105/177 TN:72/177 FP:7/32 FN: 25/32 MCC = 0.69 |
||
| Aro1 | 0 | 4.3 | 5.6 | 5.3 | Aro1 | 0 | 4.6 | 5.1 | 4.3 | ||||||
| Hyd | 4.3 | 0 | 4.4 | 5.8 | Hyd | 4.6 | 0 | 3.8 | 5.2 | ||||||
| Aro2 | 5.6 | 4.4 | 0 | 4.4 | Aro2 | 5.1 | 3.8 | 0 | 5.1 | ||||||
| HBA | 5.3 | 5.8 | 4.4 | 0 | HBA | 4.3 | 5.2 | 5.1 | 0 | ||||||
| 5 | 9-Hydroxy -Risperidone |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:112/177 TN:66/177 FN:20/32 FP:12/32 MCC = 0.69 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:123/177 TN:54/177 FN:25/32 FP:7/32 MCC = 0.69 |
||
| Aro1 | 0 | 4.3 | 6.1 | 4.4 | Aro1 | 0 | 3.6 | 5.1 | 4.3 | ||||||
| Hyd | 4.3 | 0 | 4.1 | 5.2 | Hyd | 3.6 | 0 | 4.2 | 5.2 | ||||||
| Aro2 | 6.1 | 4.1 | 0 | 4.4 | Aro2 | 5.1 | 4.2 | 0 | 7.1 | ||||||
| HBA | 4.4 | 5.2 | 4.4 | 0 | HBA | 4.3 | 5.2 | 7.1 | 0 | ||||||
| 6 | Benperidol |  |
Aro 1 | Hyd | Aro.2 | HBA | TP:120/177 TN:57/177 FP:12/32 FN:20/32 MCC = 0.66 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:122/177 TN:55/177 FP:10/32 FN:22/32 MCC = 0.66 |
||
| Aro1 | 0 | 4.6 | 5.1 | 7.4 | Aro1 | 0 | 6.2 | 5.4 | 6.8 | ||||||
| Hyd | 4.6 | 0 | 5.5 | 4.8 | Hyd | 6.2 | 0 | 4.7 | 6.2 | ||||||
| Aro2 | 5.1 | 5.5 | 0 | 4.1 | Aro2 | 5.4 | 4.7 | 0 | 4.8 | ||||||
| HBA | 7.4 | 4.8 | 4.1 | 0 | HBA | 6.8 | 6.2 | 4.8 | 0 | ||||||
| 7 | Droperidol |  |
Aro 1 | Hyd | Aro.2 | HBA | TP:119/177 TN:68/177 FP:6/32 FN:26/32 MCC = 0.70 |
 |
Aro 1 | Hyd | Aro.2 | HBA |
TP:119/177 TN:68/177 FN:24/32 FP:6/32 MCC = 0.72 |
||
| Aro1 | 0 | 5.3 | 4.2 | 4.1 | Aro1 | 0 | 4.4 | 5.6 | 5.8 | ||||||
| Hyd | 5.3 | 0 | 5.7 | 5.8 | Hyd | 4.4 | 0 | 6.3 | 4.7 | ||||||
| Aro2 | 4.2 | 5.7 | 0 | 6.1 | Aro2 | 5.6 | 6.3 | 0 | 6.0 | ||||||
| HBA | 4.1 | 5.8 | 6.1 | 0 | HBA | 5.8 | 4.7 | 6.0 | 0 | ||||||
| 8 | Nor-astemizole |  |
Aro 1 | Hyd | Aro.2 | HBA | TP:119/117 FN:26/32 FP:6/32 TN:68/117 MCC = 0.70 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:121/177 TN:56/177 FN:25/32 FP:7/32 MCC = 0.67 |
||
| Aro1 | 0 | 5.5 | 5.2 | 6.4 | Aro1 | 0 | 3.8 | 5.8 | 9.0 | ||||||
| Hyd | 5.5 | 0 | 5.1 | 3.9 | Hyd | 3.8 | 0 | 3.5 | 7.0 | ||||||
| Aro2 | 5.2 | 5.1 | 0 | 5.8 | Aro2 | 5.8 | 3.5 | 0 | 7.4 | ||||||
| HBA | 6.4 | 3.9 | 5.8 | 0 | HBA | 9.0 | 7.0 | 7.4 | 0 | ||||||
| 9 | Vesnarinone |  |
Aro 1 | Hyd | Aro.2 | HBA | TP:109/177 TN:68/177 FP:10/32 FN:22/32 MCC = 0.68 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:129/177 TN:48/177 FN:8/32 TN:24/32 MCC = 0.65 |
||
| Aro1 | 0 | 3.8 | 4.5 | 4.4 | Aro1 | 0 | 9.4 | 6.0 | NA | ||||||
| Hyd | 3.8 | 0 | 5.3 | 5.5 | Hyd | 9.4 | 0 | 4.6 | NA | ||||||
| Aro2 | 4.5 | 5.3 | 0 | 7.2 | Aro2 | 6.0 | 4.6 | 0 | NA | ||||||
| HBA | 4.4 | 5.5 | 7.2 | 0 | HBA | NA | NA | NA | 0 | ||||||
| 10 | BMLC_1835_4 |  |
Aro 1 | Hyd | Aro.2 | HBA | TP:120/177 TN:57/177 FP:24/32 FN:8/32 MCC = 0.67 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:123/177 TN:54/177 FP:25/32 FN:7/32 MCC = 0.66 |
||
| Aro1 | 0 | 4.1 | 6.5 | 5.7 | Aro1 | 0 | 3.4 | 5.8 | 3.4 | ||||||
| Hyd | 4.1 | 0 | 5.3 | 5.5 | Hyd | 3.4 | 0 | 7.5 | 5.7 | ||||||
| Aro2 | 6.5 | 5.3 | 0 | 11.5 | Aro2 | 5.8 | 7.5 | 0 | 11.9 | ||||||
| HBA | 5.7 | 5.5 | 11.5 | 0 | HBA | 3.4 | 5.7 | 11.9 | 0 | ||||||
| 11 | Resperidone |  |
Aro 1 | Hyd. | Aro.2 | HBA | TP:117/177 TN:60/177 FP:8/32 FN:24/32 MCC = 0.68 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:120/177 FP:24/32 TN:57/177 FN:8/32 MCC = 0.67 |
||
| Aro1 | 0 | 5.1 | 6.7 | 8.7 | Aro1 | 0 | 4.4 | 6.8 | 9.0 | ||||||
| Hyd | 5.1 | 0 | 5.3 | 4.5 | Hyd | 4.4 | 0 | 4.3 | 4.8 | ||||||
| Aro2 | 6.7 | 5.3 | 0 | 5.6 | Aro2 | 6.88 | 4.3 | 0 | 4.5 | ||||||
| HBA | 8.7 | 4.5 | 5.6 | 0 | HBA | 9.0 | 4.8 | 4.5 | 0 | ||||||
| 12 | Haloperidol |  |
Aro 1 | Hyd | Aro.2 | HBA | TP:130/177 TN:47/177 FP:24/32 FN:8/32 MCC = 0.64 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:132/177 TN:45/177 FP:24/32 FN:8/32 MCC = 0.66 |
||
| Aro1 | 0 | NA | 4.8 | 6.7 | Aro1 | 0 | NA | 10.1 | 6.1 | ||||||
| Hyd | NA | 0 | NA | NA | Hyd | NA | 0 | NA | NA | ||||||
| Aro2 | 4.8 | NA | 0 | 8.3 | Aro2 | 6.1 | NA | 0 | 5.6 | ||||||
| HBA | 6.7 | NA | 8.3 | 0 | HBA | 10.1 | NA | 5.6 | 0 | ||||||
| 13 | Glycerol -Nonivamide |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:120/177 TN:57/177 FP:23/32 FN:9/32 MCC = 0.67 |
 |
Aro 1 | Hyd | Aro.2 | HBA | TP:122/177 TN:55/177 FP:22/32 FN:10/32 MCC = 0.66 |
||
| Aro1 | 0 | 3.4 | 4.7 | 3.1 | Aro1 | 0 | 3.7 | 5.2 | 3.1 | ||||||
| Hyd | 3.4 | 0 | 4.4 | 4.5 | Hyd | 3.7 | 0 | 5.3 | 4.1 | ||||||
| Aro2 | 4.7 | 4.4 | 0 | 8.1 | Aro2 | 5.2 | 5.3 | 0 | 7.6 | ||||||
| HBA | 3.1 | 4.5 | 8.1 | 0 | HBA | 3.1 | 4.1 | 7.6 | 0 | ||||||
The bold values represents finally selected model.