Table 2. Molecular Dynamics Results and Inhibition Kinetics of Electric Eel AChE by QMPs.
| QMP | 1-HCl | 2-HCl | 3-HCl | 4-HCl |
|---|---|---|---|---|
| MD AS%a | 44.8 (11.8) | 50.5 (24.1) | 44.6 (6.0) | 37.4 (8.9) |
| Vmax (nM/s) | 61.2 ± 2.2 | 104.9 ± 4.2 | 80.3 ± 3.9 | 141.0 ± 8.9 |
| Km (mM) | 0.032 ± 0.014 | 0.079 ± 0.014 | 0.062 ± 0.015 | 0.189 ± 0.037 |
| Ki (mM) | 0.080 ± 0.040 | 0.095 ± 0.024 | 0.106 ± 0.042 | 1.57 ± 0.83 |
| α | 34.9 ± 22.9 | 8.7 ± 4.0 | 3.1 ± 1.7 | 1.24 ± 0.94 |
| IC50 (mM)b | 0.919 | 0.403 | 0.227 | 1.83 |
a
Over a series of 1 ns simulations, the total percentage of time ligand spent in the aged AChE active site, defined as the benzylic carbon of the QMP being 0–5 Å from the phosphylated serine residue (Supporting Information). Values of the corresponding neutral compounds are displayed in parentheses.
b
[acetylthiocholine] = 0.5 mM.