Table 2.

Estimates of the binding free energy ΔG° (kcal/mol) of various ligands to CB[7]. First, binding PMFs B(r_R) are estimated based on Eq. 23 for 100 receptor snapshots from a simulation in GBSA implicit solvent. Then $\Delta {\widehat{G}}^{\circ }$ is calculated using Eq. 22. The value in the parentheses is the standard deviation from bootstrapping: the binding free energy is estimated based on 1000 random selections of 100 binding PMFs. The experimental and Gilson columns are isothermal calorimetry measurements (ITC) and M2 calculations, respectively, taken from Moghaddam et al.³² The bottom rows are the correlation coefficient (R²) and root mean square error (RMSE, Eq. 25) with respect to the ITC and Gilson columns.

Ligand	ITC	Gilson	NAMD	M2	PB	PBSA
AD1	−14.1	−18.2	−9.4 (0.23)	−16.3 (0.15)	−17.6 (0.25)	−20.1 (0.25)
AD2	−19.4	−25.9	−27.9 (0.19)	−24.3 (0.22)	−22.9 (0.27)	−25.4 (0.26)
AD3	−20.4	−25.6	−35.7 (5.03)	−28.6 (1.87)	−23.5 (0.23)	−26.2 (0.23)
AD4	−21.5	−29.7	−40.5 (0.21)	−33.7 (0.32)	−24.3 (1.11)	−27.1 (1.06)
AD5	−19.1	−24.1	−29.5 (1.24)	−24.0 (0.20)	−22.0 (0.35)	−24.4 (0.34)
B02	−13.4	−12.0	−9.0 (0.38)	−13.7 (0.16)	−15.4 (0.26)	−18.1 (0.25)
B05	−19.5	−23.1	−38.0 (0.40)	−27.7 (0.27)	−18.6 (0.27)	−21.4 (0.27)
B11	−20.6	−22.4	−51.2 (0.34)	−37.3 (0.24)	−17.2 (0.53)	−20.5 (0.51)
F01	−12.9	−10.2	0.3 (0.82)	−0.6 (0.34)	−4.9 (0.26)	−7.6 (0.25)
F02	−16.8	−12.4	−12.0 (0.70)	−9.6 (0.75)	−11.7 (0.70)	−14.6 (0.71)
F03	−17.2	−12.2	−10.2 (0.16)	−7.3 (0.24)	−10.2 (0.22)	−13.2 (0.22)
F06	−21.0	−17.8	−24.1 (0.34)	−14.1 (0.46)	−16.2 (0.51)	−19.7 (0.52)
${\mathrm{R}}_{ITC}^2$		0.782	0.870	0.745	0.671	0.704
RMSEITC		4.6	14.0	9.0	4.4	4.5
${\mathrm{R}}_{Gilson}^2$			0.841	0.892	0.923	0.925
RMSEGilson			11.3	5.9	3.4	2.4