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Table 2 Calculated and experimental relative binding free energies between pairs of the 16 CDK2 inhibitors, corresponding to the FEP pathways depicted in Fig. 2

From: QligFEP: an automated workflow for small molecule free energy calculations in Q

Ligand Experimenta Calculatedb
FEP+ QligFEP
OPLS2005 OPLS3 OPLS2005 AMBER CHARMM
1h1q − 8.18 − 8.15 ± 0.00 − 7.56 ± 0.00
1h1r − 7.67 − 8.52 ± 0.26 − 8.61 ± 0.17 − 8.04 ± 0.11 − 7.52 ± 0.31 − 9.75 ± 0.45
1h1 s − 11.25 − 10.66 ± 0.40 − 10.14 ± 0.56 − 10.90 ± 0.28 − 11.07 ± 0.41 − 12.60 ± 0.72
1oi9 − 9.74 − 9.95 ± 0.32 − 9.66 ± 0.22 − 9.88 ± 0.16 − 10.40 ± 0.24 − 9.35 ± 0.49
1oiu − 9.08 − 10.10 ± 0.24 − 9.50 ± 0.47 − 9.89 ± 0.26 − 10.81 ± 0.74 − 11.26 ± 0.63
1oiy − 9.79 − 8.97 ± 0.29 − 8.94 ± 0.39 − 10.10 ± 0.23 − 10.82 ± 0.48 − 11.13 ± 0.52
17 − 7.04 − 8.56 ± 0.19 − 8.79 ± 0.13 − 7.99 ± 0.11 − 9.14 ± 0.51 − 10.63 ± 0.33
20 − 8.72 − 8.52 ± 0.33 − 7.96 ± 0.28 − 8.70 ± 0.18 − 8.60 ± 0.23 − 8.65 ± 0.37
21 − 7.83 − 8.50 ± 0.27 − 8.70 ± 0.15 − 7.54 ± 0.15 − 7.07 ± 0.35 − 11.11 ± 0.39
22 − 7.76 − 8.58 ± 0.23 − 9.00 ± 0.18 − 7.74 ± 0.15 − 6.68 ± 0.51 − 9.66 ± 0.47
26 − 8.43 − 9.44 ± 0.33 − 8.68 ± 0.39 − 9.57 ± 0.14 − 9.42 ± 0.44 − 10.31 ± 0.59
28 − 11.11 − 9.90 ± 0.49 − 10.31 ± 0.49 − 13.47 ± 1.10 − 5.45 ± 0.93 − 11.54 ± 0.89
29 − 9.88 − 9.53 ± 0.47 − 9.32 ± 0.61 − 13.59 ± 0.99 − 11.44 ± 1.18 − 11.55 ± 1.21
30 − 9.81 − 8.92 ± 0.38 − 9.13 ± 0.48 − 10.87 ± 0.60 − 11.48 ± 0.77 − 10.92 ± 0.50
31 − 9.54 − 8.19 ± 0.41 − 9.03 ± 0.46 − 8.75 ± 0.19 − 9.68 ± 0.48 − 10.83 ± 0.91
32 − 9.75 − 9.26 ± 0.47 − 10.27 ± 0.49 − 8.48 ± 0.84 − 9.77 ± 0.65 − 11.92 ± 0.93
R2 [95% CI]   0.48 [0.09–0.78] 0.51 [0.11–0.79] 0.59 [0.20–0.84] 0.13 [0.01–0.52] 0.33 [0.01–0.69]
MAE   0.75 (0.69c) 0.75 (0.79c) 0.85 1.11 1.54
Slope   0.43 0.44 1.17 0.53 0.56
Intercept   − 5.22 − 5.06 1.08 − 4.39 − 5.47
  1. aExperimental ∆IC50 values extracted from Ref. [71] and are transformed into ∆∆Gbind using the relation \(\Delta \Delta G_{bind,exp}^{o} = RTln\left( {\frac{{IC_{50} \left( B \right)}}{{IC_{50} \left( A \right)}}} \right)\)
  2. bAll energies are in kcal/mol, with standard error of the mean (SEM) estimated from replicate simulations for Q, and cycle closure errors for FEP+ [29]
  3. cMAE taken from Ref. [29], based on cycle closure correction