Table 2.
Predicted binding affinities of ligands to different positions in hKCC1
| Center Coordinates | Ligand | Energy, kcal/mol | RMSDlow, Å | RMSDup, Å | Y216, Å |
|---|---|---|---|---|---|
| SCl1 | ML077 | −7.6 | Best fit | Best fit | No |
| SK | −7.6 | Best fit | Best fit | No | |
| SCl2 | −8.5 | Best fit | Best fit | 3.6 | |
| SCl2 | D4.1 (25067400) | −8.2 | Best fit | Best fit | 3.5 |
| VU0463271 | −8.5 | Best fit | Best fit | 3.4 | |
| R4 (70694655) | −8.1 | Best fit | Best fit | No | |
| −7.9 | 3.405 | 5.519 | 6.6 | ||
| R5 (70696692) | −8.6 | Best fit | Best fit | No | |
| D4.6 (3228019) | −8.3 | Best fit | Best fit | No | |
| SCI2 | DIDS | −7.7 | Best fit | Best fit | No |
| −7.5 | 3.361 | 8.975 | No | ||
| −7.5 | 3.450 | 4.980 | No | ||
| H2DIDS | −7.6 | Best fit | Best fit | No | |
| SCI2 | Furosemide | −7.5 | Best fit | Best fit | 1.8 |
Coordinates were as follows: x = 109.058, y = 89.73, z = 119.906 for Cl− binding site 1 (SCl1); x = 108.077, y = 89.328, z = 116.223 for the K+ binding site (SK); x = 105.852, y = 91.041, z = 109.121 for Cl− binding site 2 (SCl2). These parameters were used as center coordinates in the docking process. Size of the surrounding box was set to 30 Å, and exhaustiveness was set at 300. Root-mean-square deviation (RMSD) values are compared with best fit; both values (low and up) are 0.000 Å for the best fit. Values in Y261 column show distance between the inhibitor and the hydroxyl group of Tyr216. Numbers in parentheses in Ligand column are PubChem Compound ID numbers. hKCC1, human K+-Cl− cotransporter.