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Table 3 Calculated and experimental shifts in binding free energies of a series of A2AAR antagonists, relative to the parent compound 11

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

Compound R Binding free energies (ΔΔGbind, kcal/mol)
Experiment FEP+a QLigFEP
11 H
25a CH3 0.25 0.53 ± 0.04 0.74 ± 0.34
25b (CH2)3CH3 − 1.15 − 0.34 ± 0.10 − 0.96 ± 0.81
25c (CH2)4CH3 − 1.56 − 0.56 ± 0.09 − 0.93 ± 0.86
25d (CH2)2Ph − 1.35 − 0.69 ± 0.11 − 0.75 ± 0.95
25e CH(CH4)2 1.39 0.88 ± 0.09 2.46 ± 0.99
25f (CH2)2CH3 0.35 0.23 ± 0.07 2.17 ± 1.07
32 H 0.06 1.24 ± 0.18 0.67 ± 0.22
41 CH3 0.56 3.08 ± 0.16 0.98 ± 0.33
R2
[95% CI]
   0.49 (0.78a)
[0.00–0.88]
0.74 (0.88b)
[0.16–0.95]
MAE    0.74 (0.68a) 0.72
Slope    0.74 0.99
Intercept    0.56 0.49
  1. aMAE reported in the original work form Lenselink et al. [30], based on cycle closure correction and using the affinity of 11 to calculate ∆G values
  2. bR2 for ∆G values using the same strategy of using ∆G with 11 as a reference