Table 1.

Measured and computed binding free energies (kcal/mol) of host OA with the six training set guest molecules. Expt: experimental data; TIP3P: computed with TIP3P¹¹; Bind3P (pred): results predicted for Bind3P by applying sensitivity analysis to simulations using TIP3P; Bind3P: results obtained by using Bind3P in new simulations. MSE: mean signed error (kcal/mol); RMSE: root-mean-squared error (kcal/mol); R²: square of Pearson correlation coefficient; m: slope of linear regression. The error metrics are averages from resampling with replacement using 10,000 bootstrap cycles, and thus may be different from the values calculated directly from the means.

Guest	Expt.	TIP3P	Bind3P (pred)	Bind3P	TIP4P-Ew	OPC	TIP4P-D
G1	−5.4	−6.5	−5.1	−5.2	−7.1	−6.1	−6.1
G2	−4.7	−5.4	−3.9	−3.8	−5.7	−5.2	−3.7
G3	−4.5	−6.8	−5.5	−5.7	−8.2	−7.8	−7.2
G4	−9.4	−12.3	−10.6	−10.6	−12.9	−11.4	−10.4
G5	−3.7	−4.5	−3.1	−3.5	−7.8	−6.4	−5.8
G6	−5.3	−6.5	−4.9	−4.8	−7.4	−6.4	−5.4
MSE		−1.5	0.0	−0.1	−2.7	−1.7	−0.9
RMSE		1.7	0.8	0.9	2.9	2.0	1.5
R2		0.8	0.8	0.8	0.6	0.6	0.6
m		1.2	1.1	1.0	0.7	0.5	0.6

The experimental binding affinities were obtained from ITC measurements⁵⁴ taken at 298 K in 50 mM sodium phosphate buffer with pH of 11.5.