Table 6.

Soft-Core Benzoquinone Free Energies (kcal/mol)

	R2-a	R2-b	R2-c	R2-d	R2-e	R2-f
R1-a	0.00 ± 0.51	1.25 ± 0.35a	−1.41 ± 0.28	−6.65 ± 0.38	−3.99 ± 0.20	0.65 ± 0.25
R1-b	0.68 ± 0.37a	1.70 ± 0.28	−0.07 ± 0.22	−6.07 ± ∞c	−3.22 ± 0.33	1.39 ± 0.22
R1-c	−1.26 ± 0.29	0.56 ± 0.33	−2.14 ± 0.23b	−8.20 ± 0.31	−4.94 ± 0.22	−0.30 ± 0.19
R1-d	−4.49 ± ∞c	−6.11 ± 0.24	−7.72 ± 0.63	−15.94 ± 0.22	−12.30 ± 0.25	−8.28 ± 0.29
R1-e	−2.58 ± ∞c	−2.09 ± 0.55	−4.73 ± 0.38	−11.39 ± 0.40	−8.04 ± 0.37	−3.98 ± 0.22
R1-f	1.57 ± ∞c	1.88 ± 1.24	0.09 ± ∞c	−8.93 ± 0.54	−5.13 ± 0.61	0.40 ± 0.37

^aThe difference between symmetric derivatives, ΔG_xy→yx, should be zero. ΔG_solvation(ab → ba) = (0.68 ± 0.37) − (1.25 ± 0.35) = −0.57 ± 0.51. Excluding da, ea, fa, and fc, the root mean square difference between symmetric derivatives is 0.71 and the root mean square precision is 0.65.

^bThe ΔG_solvation (aa → cc) value −2.14 ± 0.56 is consistent with the two substituent value of −1.99 ± 0.05 from Table 5, which was not the case with hard-core interactions.

^cNo estimate of precision could be obtained from bootstrap analysis for molecules that were not visited in all production simulations. These molecules are denoted with ±∞. The free energy estimates for these molecules are still within 0.04 to 2.16 kcal/mol of their symmetric derivatives.