Table 1.
Experimental and computed binding thermodynamics (kcal/mol) of OAH and OAMe systems. Calculated results are provided for the standard setups provided to participants (TIP3P), and for otherwise matched calculations using the OPC water model in place of TIP3P (OPC). R2 (correlation of determination) and slope were obtained from linear regression fitting. MSE: mean signed error; MUE: mean unsigned error; RMSE: root mean squared error.
| System | ΔG | ΔH | −TΔS | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Exp. | TIP3P | OPC | Exp. | TIP3P | OPC | Exp. | TIP3P | OPC | |
| OAH | |||||||||
| G1 | −5.04 ± 0.01 | −6.50 ± 0.23 | −6.09 ± 0.28 | −7.69 ± 0.01 | −8.36 ± 0.37 | −4.28 ± 0.38 | 2.64 ± 0.01 | 1.86 ± 0.44 | −1.81 ± 0.47 |
| G2 | −4.25 ± 0.01 | −5.42 ± 0.22 | −5.16 ± 0.23 | −4.39 ± 0.03 | −5.71 ± 0.29 | −1.83 ± 0.41 | 0.15 ± 0.03 | 0.29 ± 0.36 | −3.33 ± 0.47 |
| G3 | −5.06 ± 0.01 | −6.82 ± 0.23 | −7.79 ± 0.24 | −5.93 ± 0.08 | −7.16 ± 0.38 | −4.01 ± 0.41 | 0.87 ± 0.08 | 0.34 ± 0.44 | −3.78 ± 0.48 |
| G4 | −9.37± 0.00 | −12.34 ± 0.23 | −11.35 ± 0.29 | −14.80 ± 0.01 | −15.46 ± 0.38 | −9.22 ± 0.36 | 5.43 ± 0.01 | 3.12 ± 0.44 | −2.13 ± 0.46 |
| G5 | −4.50 ± 0.00 |
−4.46 ±
0.45 (−4.77 ± 0.24) |
−6.42 ± 0.25 | −9.90 ± 0.05 | −5.57 ± 0.35 | −5.60 ± 0.39 | 5.40 ± 0.05 |
1.11 ± 0.57 (0.80 ± 0.42) |
−0.82 ± 0.46 |
| G6 | −5.33 ± 0.00 | −6.46 ± 0.23 | −6.41 ± 0.32 | −5.67 ± 0.01 | −9.50 ± 0.35 | −6.82 ± 0.55 | 0.34 ± 0.01 | 3.04 ± 0.42 | 0.41 ± 0.64 |
| OAMe | |||||||||
| G1 | −5.24 ± 0.05 | −7.61 ± 0.21 | −7.88 ± 0.24 | −9.96 ± 0.01 | −11.73 ± 0.38 | −7.79 ± 0.43 | 4.72 ± 0.05 | 4.12 ± 0.43 | −0.09 ± 0.49 |
| G2 | −5.04 ± 0.03 | −6.99 ± 0.30 | −6.97 ± 0.33 | −7.56 ± 0.10 | −10.67 ± 0.33 | −6.72 ± 0.39 | 2.52 ± 0.11 | 3.68 ± 0.45 | −0.25 ± 0.51 |
| G3 | −5.94 ± 0.12 | −7.34 ± 0.22 | −8.82 ± 0.24 | −6.62 ± 0.18 | −9.46 ± 0.42 | −6.94 ± 0.32 | 0.68 ± 0.22 | 2.12 ± 0.47 | −1.88 ± 0.40 |
| G4 | −2.38 ± 0.02 | −4.35 ±
0.28 (−1.99 ± 0.23) |
−5.67 ±
0.32 (−0.60 ± 0.27) |
- | −13.68 ± 0.34 | −5.71 ± 0.42 | - |
9.33 ±
0.44 (11.69 ± 0.41) |
0.04 ± 0.53 (5.11 ± 0.50) |
| G5 | −3.90 ± 0.02 | −5.30 ± 0.22 | −6.64 ± 0.24 | - | −6.87 ± 1.03 | −7.17 ± 0.45 | - | 1.57 ± 1.05 | 0.53 ± 0.51 |
| G6 | −4.52 ± 0.02 | −6.02 ± 0.21 | −7.04 ± 0.25 | −9.05 ± 0.13 | −11.03 ± 0.37 | −7.25 ± 0.44 | 4.54 ± 0.13 | 5.01 ± 0.43 | 0.21 ± 0.51 |
| Error statistics | |||||||||
| R2 | 0.83 ± 0.15 (0.90 ± 0.10) |
0.68 ± 0.22 (0.77 ± 0.16) |
0.51 ± 0.30 | 0.50 ± 0.21 | 0.28 ± 0.22 (0.26 ± 0.23) |
0.23 ± 0.22 (0.23 ± 0.22) |
|||
| Slope | 1.19 ± 0.22 (1.45 ± 0.17) |
0.89 ± 0.25 (1.45 ± 0.47) |
0.64 ± 0.34 | 0.53 ± 0.22 | 0.37 ± 0.26 (0.35 ± 0.27) |
0.27 ± 0.25 (0.27 ± 0.25) |
|||
| MSE | −1.59 ±
0.22 (−1.42 ± 0.25) |
−2.14 ±
0.23 (−1.72 ± 0.37) |
−1.31 ± 0.68 | 2.11 ± 0.62 | −0.26 ±
0.61 (−0.29 ± 0.63) |
−4.07 ±
0.65 (−4.08 ± 0.64) |
|||
| MUE | 1.62 ± 0.20 (1.49 ± 0.22) |
2.14 ± 0.23 (2.01 ± 0.21) |
2.18 ± 0.40 | 2.41 ± 0.50 | 1.48 ± 0.40 (1.51 ± 0.42) |
4.13 ± 0.61 (4.14 ± 0.61) |
|||
| RMSE | 1.74 ± 0.20 (1.65 ± 0.21) |
2.28 ± 0.21 (2.13 ± 0.19) |
2.49 ± 0.40 | 2.84 ± 0.53 | 1.89 ± 0.48 (1.95 ± 0.51) |
4.52 ± 0.57 (4.53 ± 0.57) |
|||
| τ | 0.67 ± 0.13 (0.68 ± 0.13) |
0.55 ± 0.18 (0.58 ± 0.18) |
0.44 ± 0.27 | 0.46 ± 0.24 | 0.23 ± 0.23 (0.22 ± 0.23) |
0.14 ± 0.26 (0.14 ± 0.26) |
|||
Experimental binding free energies (ΔG) and enthalpies (ΔH) are reported as mean ± standard error of the mean (SEM).
The experimental binding data were obtained from Dr. Bruce Gibb [38]. All binding enthalpies and binding affinities of OAH-G6, OAMe-G6 and OAH-G4 were measured by ITC at 298 K in 50 mM sodium phosphate buffer with a pH of 11.5. The binding free energies of the rest systems were measured by NMR at 298 K in 10 mM sodium phosphate with a pH of 11.3 except that OAMe-G4 was measured at 278 K. The same experimental affinities were used for the error analysis in the SAMPL5 overview paper [39].
For binding free energies and entropy terms, values in bold are the corrected affinities of OAH-G5 and OAMe-G4, while values inside the parentheses are based on the submitted predictions. Note that the binding enthalpies are not affected by sampling problems along the pulling pathway because the enthalpy calculations do not depend on the pulling pathway.
The error statistics R2, slope, MSE, MUE, RMSE and τ are, respectively, the Pearson coefficient of determination, linear regression slope, mean signed error, mean unsigned error and Kendall rank correlation coefficient, respectively. The mean values and uncertainties of the error metrics were obtained through resampling with replacement.