Table 2. LIE-Calculated and Experimental Binding Free Energies of Sulfonamide Inhibitors in Complex with IRAPa,b.
| LIEb |
|||
|---|---|---|---|
| ligand | pose Ac | pose Bd | experimental from IC50 |
| 8 | –7.70 ± 0.1 | –8.08 ± 0.2 | –8.10 ± 0.1 |
| 11 | –8.44 ± 0.4 | –7.54 ± 0.2 | –6.72 ± 0.1 |
| 12 | –8.22 ± 0.2 | –7.85 ± 0.2 | >−4.09e |
| 13 | –7.64 ± 0.1 | –8.20 ± 0.1 | –8.32 ± 0.1 |
| 14 | –7.44 ± 0.2 | –7.15 ± 0.2 | >−5.45f |
| 15 | –7.04 ± 0.2 | –7.04 ± 0.2 | >−5.45f |
| 16 | –6.88 ± 0.2 | –7.38 ± 0.2 | –6.60 ± 1.3 |
| 17 | –7.57 ± 0.2 | –7.51 ± 0.1 | –7.13 ± 0.2 |
| 18 | –7.35 ± 0.3 | –7.48 ± 0.1 | –6.76 ± 0.1 |
| 19 | –7.46 ± 0.3 | –7.12 ± 0.1 | –6.67 ± 0.2 |
| 20 | –7.66 ± 0.2 | –7.14 ± 0.2 | >−4.09e |
| 21 | –8.08 ± 0.2 | –8.52 ± 0.2 | –8.70 ± 0.1 |
| 22 | –7.62 ± 0.2 | –7.44 ± 0.1 | –6.98 ± 0.1 |
| 23 | –7.26 ± 0.1 | –7.05 ± 0.1 | –7.17 ± 0.1 |
| 24 | –7.64 ± 0.2 | –7.81 ± 0.1 | –7.97 ± 0.1 |
| 25 | –7.43 ± 0.1 | –7.34 ± 0.1 | –8.36 ± 0.0 |
| 26 | –7.51 ± 0.1 | –7.49 ± 0.2 | –8.54 ± 0.1 |
| 27 | –8.04 ± 0.1 | –8.39 ± 0.1 | –8.07 ± 0.2 |
| 28 | –7.45 ± 0.2 | –6.89 ± 0.1 | –7.34 ± 0.1 |
| 29 | –7.34 ± 0.3 | –7.25 ± 0.2 | –8.29 ± 0.1 |
| 30 | –7.43 ± 0.1 | –7.47 ± 0.1 | –7.67 ± 0.1 |
| 31 | –7.78 ± 0.2 | –8.00 ± 0.2 | –7.67 ± 0.0 |
| 32 | –7.77 ± 0.1 | –6.96 ± 0.1 | –6.99 ± 0.0 |
| 33 | –6.91 ± 0.2 | –6.41 ± 0.2 | –6.61 ± 0.0 |
| 34 | –6.94 ± 0.3 | –6.99 ± 0.2 | –6.70 ± 0.2 |
a
Calculations based on pose A and pose B.
b
All energies are in kcal/mol, with standard error of the mean (SEM) for calculated (replicate simulations) and experimental (independent experiments) values.
c
Optimized LIE model, with α = 0.181, β = 0.1, γ = −6.43 for pose A.
d
α = 0.181, β = 0.07, and γ = −4.89 for pose B.
e
Experimental IC50 is >1000 μM,
f
Experimental IC50 is >100 μM. Neutral compounds 9–10, which are also inactive, are excluded from the table as they do not obey our LIE parameterization derived for charged compounds.