Table 2.

Calculated binding free energies (kcal/mol) compared to the corresponding experimental binding free energies (kcal/mol, derived from the experimental K_i shown in Figure 1 or 2).

Liganda	ΔG(CB1R)			ΔG(CB2R)			ΔG(CB1R)-ΔG(CB2R)
	ΔGPBb	ΔGcorrc	ΔGexpd	ΔGPBb	ΔGcorrc	ΔGexpd	ΔΔGcorrc,e	ΔΔGexpf
ACEA52	−39.07	−12.08	−12.15	−18.19	−7.60	−7.82	−4.98	−4.33
O-186027	−38.44	−11.97	−11.88	−19.30	−7.96	−6.86	−4.54	−5.02
ACPA53	−36.78	−11.67	−11.88	−24.95	−9.79	−8.44	−2.68	−3.45
O-181227	−35.54	−11.44	−11.62	−18.06	−7.56	−7.43	−4.12	−4.20
AM88153	−35.45	−11.43	−11.36	−26.78	−10.38	−9.64	−1.87	−1.72
AM88354	−35.10	−11.36	−10.99	−25.48	−9.96	−9.12	−2.11	−1.86
VJ-11528	−21.05	−8.82	−7.52	−25.19	−9.86	−8.60	1.39	1.08
R-Methanandamide53	−29.66	−10.38	−10.57	−22.18	−8.89	−8.36	−1.57	−2.21
2-AG53	−29.28	−10.31	−9.93	−24.23	−9.55	−9.39	−0.95	−0.54
Anandamide53	−27.69	−10.02	−9.90	−19.37	−7.98	−7.84	−1.79	−2.06
AM117455	−25.09	−9.55	−9.53	−16.34	−7.00	−7.48	−1.89	−2.05
O-181127	−24.13	−9.38	−9.52	−19.74	−8.10	−8.37	−0.79	−1.16
S-Methanandamide25	−23.83	−9.32	−9.28	−19.40	−7.99	−6.98	−0.80	−2.30
PNR-4-2028	−25.79	−9.67	−9.33	−26.52	−10.29	−12.00	0.52	2.67
PNR-4-0428	−25.22	−9.57	−9.43	−25.84	−10.07	−10.89	0.49	1.46
PNR-4-0228	−27.64	−10.01	−9.80	−27.78	−10.70	−10.57	0.37	0.77
PNR-4-0528	−21.95	−8.98	−8.85	−24.10	−9.51	−9.83	0.88	0.98
PNR-4-9928	−25.28	−9.58	−9.54	−25.78	−10.06	−9.81	0.46	0.28
PNR-9-3328	−16.18	−7.93	−7.60	−23.26	−9.24	−9.55	2.13	1.95
PNR-4-0328	−28.42	−10.15	−9.63	−23.26	−9.24	−9.57	−0.98	−0.06
PNR-4-1528	−28.18	−10.11	−9.96	−20.72	−8.42	−9.53	−1.57	−0.43
PNR-4-1728	−16.52	−7.99	−8.26	−19.31	−7.96	−8.55	1.04	0.29
RMSD (kcal/mol)		0.35			0.75		0.75

^aThe subscript after the ligand name refers to the reference for the experimental K_i (shown in Figure 1 or 2) used to derive the experimental binding free energy.

^bCalculated binding free energies obtained from the MM-PBSA calculations without any empirical correction.

^cCalculated binding free energies after empirical correction using Eq. (1), (2), or (3).

^dThe experimental binding free energy was converted from the experimental K_i using the well-known thermodynamic equation: ΔG_exp = −RTln (K_i).

^eΔΔG_corr is the corrected binding free energy difference (ΔG(CB₁R) −ΔG(CB₂R)).

^fΔΔG_exp = −RTln (K_i (CB₁R)/K_i(CB₂R)) = ΔG_exp(CB₁R) −ΔG_exp(CB₂R).