Table 1.

Absolute binding free energy values for OAH-guest and OAMe-guest complexes (in kcal mol⁻¹)

Complex	$\Delta G_{bind}^{TI}$	$\Delta G_{bind}^{TI-ps}$	$\Delta G_{bind}^{HBAR}$	$\Delta G_{bind}^{HBAR-ps}$	$\Delta G_{bind}^{HBAR-ps1}$	$\Delta G_{bind}^{HBAR-ps2}$	$\Delta G_{bind}^{all}$	$\Delta G_{bind}^{ITC}$	$\Delta G_{bind}^{NMR}$	$\Delta G_{bind}^{ave}$†
OAH–G1	−7.6 ± 0.7	−4.5 ± 0.6	−6.4 ± 0.7	−4.5 ± 0.2	−4.2 ± 1.0	−4.5 ± 0.2	−3.4 ± 1.1	−5.40	−5.05	−5.22
OAH–G2	−2.7 ± 0.7	−2.7 ± 0.7	−3.2 ± 0.2	−3.2 ± 0.2	−2.2 ± 0.2	−3.2 ± 0.2	−2.7 ± 0.3	−4.73	−4.26	−4.49
OAH–G3	−4.8 ± 1.1	−4.5 ± 1.2	−3.4 ± 0.0	−3.4 ± 0.0	−3.4 ± 0.0	−3.4 ± 0.0	−4.0 ± 0.5	−4.50	−5.07	−4.78
OAH–G4	−8.1 ± 1.5	−7.8 ± 1.3	−5.0 ± 0.1	−5.0 ± 0.1	−5.0 ± 0.1	−4.4 ± 0.5	−5.5 ± 1.1	−9.38	–	−9.38
OAH–G5	−1.7 ± 0.1	−1.6 ± 0.5	−1.7 ± 0.1	−1.6 ± 0.5	−1.6 ± 0.5	−1.6 ± 0.5	−1.6 ± 0.5	−3.73	−4.51	−4.12
OAH–G6	−4.9 ± 1.5	−4.9 ± 1.5	−4.1 ± 0.1	−4.1 ± 0.1	−4.1 ± 0.1	−4.1 ± 0.1	−4.5 ± 0.2	−5.34	−4.91	−5.12
RMSD*	1.6	1.4	2.2	2.2	2.3	2.4	2.1
r*	0.7	0.9	0.4	0.7	0.7	0.5	0.8
τ*	1.0	0.8	0.8	1.0	1.0	0.8	0.7
OAMe–G1	−6.1 ± 0.9	−4.2 ± 0.8	−6.4 ± 0.7	−6.4 ± 0.7	−4.2 ± 0.4	−4.2 ± 0.0	−3.7 ± 0.5	−5.47	−5.25	−5.36
OAMe–G2	−7.1 ± 0.6	−7.1 ± 0.6	−5.3 ± 0.3	−5.3 ± 0.3	−5.3 ± 0.3	−4.7 ± 0.3	−6.1 ± 1.1	−5.26	−5.05	−5.15
OAMe–G3	−6.5 ± 1.5	−6.5 ± 1.5	−6.5 ± 1.5	−6.5 ± 1.5	−6.5 ± 1.5	−6.5 ± 1.5	−6.5 ± 1.5	−5.74	−5.96	−5.85
OAMe–G4	−9.9 ± 2.4	−9.9 ± 2.4	−10.5 ± 1.0	−10.5 ± 1.0	−10.5 ± 1.0	−6.6 ± 0.3	−7.8 ± 1.2	–	−2.38	−2.38
OAMe–G5	−2.6 ± 0.6	−2.6 ± 0.6	−2.9 ± 0.7	−2.9 ± 0.7	−2.6 ± 0.6	−2.6 ± 0.6	−2.6 ± 0.6	−	−3.91	−3.91
OAMe–G6	−7.0 ± 0.3	−7.0 ± 0.3	−7.0 ± 0.3	−7.0 ± 0.3	−7.0 ± 0.3	−5.3 ± 1.0	−6.0 ± 0.5	−4.52	−4.45	−4.48
RMSD*	3.4	3.4	3.5	3.5	3.5	1.9	2.5
r*	−0.3	−0.4	−0.4	−0.4	−0.5	0.0	−0.2
τ*	−0.2	−0.2	0.0	0.0	−0.2	0.0	0.0
MSD**	−1.2	−0.7	−0.6	−0.5	−0.1	0.3	0.0
MAD**	2.3	2.2	2.3	2.3	2.4	1.9	2.2
RMSDtot **	3.1	3.0	3.2	3.1	3.2	2.4	2.7

Rows 2–7 pertain to OAH-guest complexes and rows 9–14 correspond to OAMe-guest complexes. We included the root mean square deviation for each set (RMSD), the overall mean signed deviation (MSD) and mean absolute deviation (MAD) and the root mean square deviation for each method (RMSD^tot)

^†Average experimental value from ITC and NMR experiments. The NMR data are missing the OAH-G4 binding free energy, and the ITC data are missing OAMe-G4 and OAMe-G5 binding free energies

^*RMSD, Pearson’s coefficient (r) and Kendall rank coefficient (τ) computed with respect to the average of the two experimental sets

^**MSD, MAD and RMSD^tot computed with respect to the average of the two experimental sets