Table 8.
Performance of the various methods to calculate relative binding free energies (MAD and maximum error, Max, in kJ/mol) compared to experimental results [23]
| GScore | MM/GBSA | QM/MM | FES | ||
|---|---|---|---|---|---|
| Set 1 | |||||
| MAD | 5.8–6.1 | 20.8–26.3 | 17.6–29.1 | 10.9–15.9 | |
| R | −0.58 to 0.03 | −0.69 to −0.60 | −0.42 to −0.01 | −0.80 to −0.54 | |
| τ | −1.00 to −0.40 | −0.43 to 0.00 | −0.14 to 0.50 | −1.00 to −0.71 | |
| Max | 10.2 | 32.2–50.4 | 33.3–66.8 | 23.3 | |
| 2WI7 | 3FT5 | ||||
|---|---|---|---|---|---|
| Set 2 without Wat1/2 | |||||
| MAD | 7.7 | 27.8 | 12.9 | 14.2 ± 1.0 | 5.3 ± 0.8 |
| R | −0.57 | −0.81 | 0.43 | −0.81 ± 0.07 | 0.59 ± 0.10 |
| τ | −1.00 | −1.00 | −0.33 | −0.33 ± 0.33 | 0.33 ± 0.48 |
| Max | 16.4 | 45.6 | 19.9 | 26.0 ± 1.8 | 11.2 ± 1.8 |
| 2WI7 | 3FT5 | ||||
|---|---|---|---|---|---|
| Set 2 with Wat1/2 | |||||
| MAD | 6.1 | 41.0 | 4.8 ± 1.3 | 3.7 ± 1.3 | |
| R | 0.49 | −0.58 | 1.00 ± 0.04 | 1.00 ± 0.04 | |
| τ | 0.33 | 0.33 | 0.33 ± 0.43 | 0.33 ± 0.43 | |
| Max | 15.2 | 60.2 | 6.1 ± 1.8 | 4.1 ± 1.8 | |
| Set 3 | |||||
| MAD | 4.7–10.4 | 29.6–56.0 | 23.6–47.1 | 8.7–14.6 | |
| R | −0.45 to 0.70 | 0.18 to 0.92 | −0.32 to 0.57 | −0.47 to −0.20 | |
| τ | −0.56 to 0.33 | 0.33 to 0.78 | −0.33 to 0.56 | −0.78 to 0.11 | |
| Max | 8.8–16.9 | 55.4–95.6 | 59.1–88.4 | 17.9–27.9 | |
For set 1, the reported values are the range obtained when doing three comparisons: four relative affinities using ligand 82 as the reference, all seven relative affinities that can be obtained by combining two perturbations, or all ten possible relative affinities of the five ligands. For set 2, we present the results of the three perturbations studied by FES, reporting bootstrapped uncertainties, using the observed standard error for FES. Values in brackets for GScore and MM/GBSA were obtained using the 2WI7 crystal structure. For set 3, we present the range obtained by using either ligands 10, 11, 23, 26, 28, or 34 as the reference