Table 4. Experimental and calculated binding free energies, average binding energies and reorganization free energies of the (-)-stepholidine C3 analogues with and without enclosed hydration corrections.

Compound	$\Delta G_{\text{exp}}^{°}$a,b	Without enclosed hydration model			With enclosed hydration model
		$\Delta G_{\text{calc}}^{°}$b,c	ΔEbb,c	$\Delta G_{\text{reorg}}^{°}$b,c	$\Delta G_{\text{calc}}^{°}$b,c	ΔEbb,c	$\Delta G_{\text{reorg}}^{°}$b,c
1a	−10.1	−2.2	−36.9	34.7	−8.8	−42.5	33.7
1b	−10.0	−2.3	−38.0	35.7	−10.4	−44.7	34.3
1c	−10.0	−1.8	−40.3	38.5	−11.5	−48.1	36.6
1d	−10.2	−0.3	−43.7	43.4	−10.6	−55.6	45.0
1e	−10.4	−3.9	−39.6	35.7	−12.5	−55.2	42.7
1f	−9.6	−3.1	−32.7	29.6	−8.9	−43.2	34.3
RMSEb,d		7.9			1.2
Correlation coefficient (r)		−0.014			0.64

^a Experimental affinities are calculated using the relation $\Delta G_{\text{exp}}^{°}=k_{B}Tln{K}_i$ where K_i is the inhibition constant of binding, k_B is the Boltzmann’s constant.

^bIn kcal/mol.

^cApproximate uncertainties for all measurements are implied by the number of significant figures; the actual values of the uncertainties for each measurement are provided in Table A in S1 File.

^dRoot mean square error relative to the experimental binding free energies.