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

Table 3 Calculated and experimental shifts in binding free energies of a series of A_2AAR antagonists, relative to the parent compound 11

Compound	R	Binding free energies (ΔΔG_bind, kcal/mol)
Compound	R	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 (0.78^a) [0.00–0.88]	0.74 (0.88^b) [0.16–0.95]
MAE			0.74 (0.68^a)	0.72
Slope			0.74	0.99
Intercept			0.56	0.49

^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
^bR² for ∆G values using the same strategy of using ∆G with 11 as a reference

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