TABLE 2.

Comparison of a) relative and b) absolute binding free energy differences calculated with transformato, pmx/CGenFF, FEP+ and AMBER-TI with experiment. The root mean squared error (RMSE), the mean absolute error (MAE), both in kcal/mol, as well as the Pearson’s correlation coefficient R, and the Spearman’s rank correlation coefficient ρ are listed. For the ΔΔG ^bind results obtained with transformato in a) we also report bootstrapped error estimates for RMSE, MAE, R and ρ.

a) ΔΔG bind
Transformato					pmx/CGenFF a		FEP + b		AMBER-TI
system	RMSE	MAE	R	ρ	RMSE	MAE	RMSE	MAE	RMSE	MAE
overall	1.18	0.87	0.57	0.48
	[0.98; 1.38]	[0.72; 1.02]	[0.36; 0.71]	[0.29; 0.64]
JNK1	0.91	0.68	0.34	0.32	0.95	0.68	1.02	0.78	1.45 c	1.15 c
	[0.64; 1.17]	[0.51; 0.86]	[-0.02; 0.66]	[-0.02; 0.63]
FXa	1.23	1.01	0.83	0.71					1.11  d	0.72  d
	[0.77; 1.69]	[0.70; 1.41]	[0.40; 0.95]	[0.22; 0.99]
GAL3	0.58	0.50	0.76	0.57	0.61	0.54
	[0.39; 0.73]	[0.32; 0.68]	[0.08; 0.94]	[-0.17; 0.96]
CDK2	1.12	0.80	0.63	0.59	1.13	0.84	1.16	0.95	1.16 e	0.94 e
	[0.69; 1.46]	[0.46; 1.17]	[0.28; 0.88]	[0.08; 0.92]
TYK2	1.74	1.37	0.42	0.21	1.61	1.33	0.95	0.74	1.29 c	1.07 c
	[1.26; 2.15]	[0.95; 1.83]	[-0.16; 0.72]	[-0.02; 0.63]

b) ΔG bind
system	Transformato			pmx/CGenFF a			FEP + b			AMBER-TI
ΔG	RMSE	MAE	R	RMSE	MAE	R	RMSE	MAE	R	RMSE	MAE	R
overall	1.17	0.85	0.73
JNK1	0.81	0.57	0.60	0.81	0.57	0.66	1.14	1.06	0.85	1.45 c	1.07 c	0.22 c
FXa	1.04	0.92	0.76							0.96 d	0.66 d	0.83 d
GAL3	0.90	0.69	0.59	0.50	0.43	0.90
CDK2	1.12	0.80	0.61	1.14	0.89	0.41	0.95	0.82	0.52	0.84 e	0.72 e	0.74 e
TYK2	1.74	1.37	0.42	1.87	1.61	0.53	0.58	0.46	0.88	1.27 c	1.07 c	0.49 c

^a Gapsys et al. (2020), ^b Wang et al. (2015), ^c Song et al. (2019), ^d Hu et al. (2016), ^e He et al. (2020).