TABLE 4.
Molecular docking and stability of DM490, DM497, and PAM-4 at different subunit interfaces and the ion channel of the α1β2γ2 GABAAR model
| Docking site | DM490 | DM497 | PAM-4 | |||
|---|---|---|---|---|---|---|
| TBE (kcal/mol) | RMSD (VAR) | TBE (kcal/mol) | RMSD (VAR) | TBE (kcal/mol) | RMSD (VAR) | |
| β+/α− (anesthetic)* | −42 | 2.9 (0.1) | −43 | 7.1 (0.1) | −36 | 3.9 (0.2) |
| α+/β− (anesthetic) | −38 | 5.1 (0.1) | −38 | 11.3 (1.0) | −38 | 13.9 (1.0) |
| γ+/β− (anesthetic) | −35 | 5.7 (1.6) | −39 | 4.9 (0.1) | −32 | 12.4 (0.8) |
| α+/γ− (orphan) | −41 | 17.5 (16.3) | −40 | 8.0 (0.1) | −29 | 4.1 (0.9) |
| Ion channel | −40 | 3.7 (0.4) | −34 | 11.1 (2.9) | −27 | 5.2 (0.1) |
TBE, theoretical binding energy (kcal/mol).
More negative values indicate higher binding affinity.
Depending on the RMSD VAR values, measured during the last third of the MDs, the observed interactions were considered stable (RMSD VAR < 0.2), nearly stable (RMSD VAR 0.2–2), and unstable (RMSD VAR > 2).
*Stable interaction within the (γ+)β+/α− interface.