Table 2. Summary of the free energy calculation results based on docking. Shown are the data for the predicted most stable binding poses for each ligand. ΔGcalc is the calculated standard binding free energy; ΔGexp is the experimental standard binding free energy. For comparison, also the affinities predicted with the docking scoring function are reported. All values are in kcal mol–1. All errors are one standard deviation. “X-ray pose” indicates whether the lowest energy pose identified corresponds to the crystallographically observed binding mode; also the RMSD of the pose as compared to the crystal is reported. αThis is an estimate of the typical ITC standard deviation (1σ) based on the variability of the affinity values observed in the ABRF-MIRG′02 inter-laboratory assessment;67βthe error represents the standard deviation of two measurements; γno error reported as only a single experiment was performed. Difference values may include rounding effects.
| Compound | ΔGcalc | ΔGexp | ΔGcalc–ΔGexp | X-ray pose | RMSD (Å) | Docking ΔG |
| 1 | –10.9 ± 0.8 | –9.8 ± 0.1α | –1.1 ± 0.8 | Yes | 3.2 | –2.7 |
| 2 | –10.1 ± 0.4 | –9.6 ± 0.1α | –0.5 ± 0.4 | Yes | 1.9 | –4.7 |
| 3 | –10.8 ± 0.2 | –9.0 ± 0.1α | –1.8 ± 0.2 | Yes | 2.0 | –4.9 |
| 4 | –9.0 ± 0.8 | –8.9 ± 0.1α | –0.0 ± 0.8 | Yes | 1.8 | –3.4 |
| 5 | –8.3 ± 0.2 | –8.8 ± 0.1β | +0.5 ± 0.2 | Yes | 1.2 | –4.2 |
| 6 | –10.6 ± 0.3 | –8.2 ± 0.1α | –2.4 ± 0.3 | No | 5.0 | –4.6 |
| 7 | –6.6 ± 0.3 | –7.8 ± 0.1α | +1.2 ± 0.3 | Yes | 2.2 | –5.2 |
| 8 | –10.2 ± 0.2 | –7.4 ± 0.1α | –2.8 ± 0.2 | Yes | 0.8 | –4.2 |
| 9 | –7.7 ± 0.1 | –7.3 ± 0.0β | –0.5 ± 0.1 | Yes | 1.8 | –4.2 |
| 10 | –6.2 ± 0.1 | –6.3 ± 0.1β | +0.1 ± 0.2 | Yes | 0.7 | –3.2 |
| 11 | –5.4 ± 0.1 | –5.6γ | +0.2 ± 0.1 | n.a. | n.a. | –4.8 |
| Statistics | |
| Mean absolute error | 1.0 ± 0.1 |
| Root mean square error | 1.4 ± 0.1 |
| Pearson's r | 0.77 ± 0.04 |
| Spearman's ρ | 0.72 ± 0.08 |