Table 4.

The binding free energy (kcal/mol) and its decomposition for the test set

System	Structurea	ΔΔGrep	ΔΔGdis	ΔΔGelec	ΔΔGt,r,c	$\mathrm{\Delta }{G}_{\text{b}}^{\circ }$	expt
T-1	Crystal	−13.74 ± 2.06	−14.68 ± 0.79	3.02 ± 0.35	11.31 ± 0.70	−14.10 ± 2.64	−9.41b
	Docking (cog)	−19.67 ± 2.26	−6.55 ± 0.23	4.75 ± 0.72	9.44 ± 0.42	−12.04 ± 2.13
	Docking (ncog)	−15.60 ± 2.55	−9.28 ± 0.71	3.75 ± 0.29	8.59 ± 0.29	−12.54 ± 1.88
T-2	Crystal	−15.87 ± 0.87	−14.07 ± 0.22	−4.42 ± 0.27	13.17 ± 0.21	−21.20 ± 0.90	−9.74c
	Docking (cog)	−15.99 ± 1.27	−16.24 ± 0.27	−2.66 ± 0.56	11.64 ± 0.13	−23.25 ± 1.35
	Docking (ncog)	−13.00 ± 1.60	−12.27 ± 0.41	−2.61 ± 0.15	9.36 ± 0.12	−18.51 ± 1.40
T-3	Crystal	−13.80 ± 1.32	−14.62 ± 0.47	0.35 ± 0.43	9.40 ± 0.03	−18.66 ± 1.72	−8.11b
	Docking (cog)	−14.75 ± 2.00	−15.16 ± 0.31	−0.46 ± 0.36	11.42 ± 0.17	−18.95 ± 1.60
	Docking (ncog)	−12.70 ± 1.28	−14.01 ± 0.31	2.58 ± 0.08	9.95 ± 0.19	−14.19 ± 1.62
T-4	Crystal	−12.71 ± 2.03	−11.60 ± 0.55	−1.41 ± 0.37	9.41 ± 0.25	−16.31 ± 2.56	−8.29d
	Docking (cog)	−12.98 ± 0.40	−12.32 ± 0.25	−1.87 ± 0.29	11.29 ± 0.46	−15.88 ± 0.52
	Docking (ncog)	−11.90 ± 1.72	−10.99 ± 0.53	−2.00 ± 0.11	8.49 ± 0.16	−16.41 ± 1.97
X-1	Crystal	−14.00 ± 2.84	−8.99 ± 0.55	4.01 ± 0.25	11.46 ± 0.93	−7.52 ± 3.67	−6.81d
	Docking (cog)	−16.15 ± 0.46	−7.47 ± 0.36	3.50 ± 0.40	10.34 ± 2.00	−9.78 ± 2.12
X-2e	MDMX/K23 Model	−11.03 ± 1.53	−10.25 ± 0.54	2.69 ± 0.59	10.79 ± 0.20	−7.80 ± 1.04	−6.10d

^aCrystal: crystal structure, Docking (cog): Docking model with near-native ligand pose from cognate-receptor docking, Docking (ncog): Docking model with near-native ligand pose from noncognate-receptor docking.

^bΔG_exp calculated using IC50

^cΔG_exp calculated using K_b

^dΔG_exp calculated using K_i

^eSystem X-2 is a model structure of MDMX in complex with the ligand (K23 in Figure 1) in system T-4. The starting structure of system X-2 was generated by modifying the crystal structure of system X-1.