Table 4.

Comparison of experimental and calculated binding free energies (ΔG°) using four different water models for the host OA with guests (all in kcal/mol except for R² and m, which are unitless). The uncertainties of the computed ΔG° values range from 0.2 to 0.3 kcal/mol. The uncertainties in RMSE and MSE are 0.3–0.4 kcal/mol and 0.1–0.3 kcal/mol, respectively, based on bootstrap resampling. Experiments were done with ITC or NMR, as indicated. MSE: mean signed error; RMSE: root-mean-squared error; R²: coefficient of determination, i.e., the square of the Pearson correlation coefficient; m: slope of linear regression. The error metrics are averages over 10,000 bootstrap cycles of sampling with replacement, and thus may be different from the values calculated directly from the means.

Guest	Expta	Bind3P	TIP3P	TIP4P-Ew	OPC	TIP4P-D
L1	−8.3	−13.1	−14.2	−14.7	−13.3	−12.7
L2	−7.4	−12.4	−13.2	−13.6	−12.6	−12.2
L3	−4.9	−7.2	−8.7	−9.1	−8.8	−7.6
L4	−6.0	−8.8	−10.8	−11.9	−10.8	−10.2
L5	−6.9	−10.1	−11.1	−12.8	−12.1	−11.3
O1	−3.7	−4.0	−5.3	−5.7	−5.4	−4.6
O2	−5.9	−7.5	−9.4	−10.1	−9.9	−8.9
O3	−6.3	−7.7	−10.3	−11.1	−10.6	−9.7
O4	−6.7	−7.7	−9.3	−10.4	−9.9	−9.2
O5	−5.2	−5.1	−7.5	−8.2	−7.1	−6.6
O6	−5.6	−7.8	−9.2	−9.7	−9.3	−8.3
O7	−7.6	−8.4	−10.4	−10.9	−10.2	−9.5
O8	−3.7	−5.5	−7.3	−7.8	−6.9	−6.0
O9	−6.6	−9.3	−11.0	−11.2	−10.2	−9.3
MSE		−2.1	−3.8	−4.5	−3.7	−2.9
RMSE		2.6	4.0	4.6	3.9	3.2
R2		0.7	0.7	0.7	0.7	0.7
m		1.4	1.4	1.4	1.3	1.4

^aThe experimental ΔG° values were obtained from references⁶² (L1–L5) and⁴⁵ (O1–O9). The L set in 50mM sodium tetraborate at pH 8.9, and the O set in10 mM sodium tetraborate buffer at pH 9.2 for both NMR and ITC. All measurements were done at 298 K.