Table 5. Comparison of Solvation Free Energy Differences in kcal/mol from Absolute and Alchemical Transformations Using Alternative Approaches^a.

Transformation	ΔΔGsolv	ΔΔGsolvabs	ΔΔGsolv – ΔΔGsolvabs	pb	ΔΔGsolvc
HEX2PRP-2d	–0.50 ± 0.05	–0.49 ± 0.06	–0.01 ± 0.08	0.78	–0.47 ± 0.04
TOL2PYR-2	–4.67 ± 0.02	–4.67 ± 0.04	0.00 ± 0.04	1.00	–4.69 ± 0.02
HEX2POL-2d	–7.09 ± 0.05	–7.11 ± 0.07	0.02 ± 0.09	0.62	–7.09 ± 0.04
PRP2DIM-2	–3.36 ± 0.02	–3.36 ± 0.03	0.00 ± 0.04	1.00	–3.33 ± 0.02
PRP2DIM-3	–3.34 ± 0.02	–3.36 ± 0.03	0.02 ± 0.04	0.25	–3.33 ± 0.02
ETH2MTA-2d	–5.91 ± 0.02	–5.87 ± 0.02	–0.04 ± 0.03	0.01	–5.90 ± 0.02
MET2AMM-2	–6.05 ± 0.02	–6.19 ± 0.02	0.14 ± 0.03	0.00	–6.22 ± 0.02
MET2AMM-3d	–5.60 ± 0.02	–6.19 ± 0.02	0.59 ± 0.03	0.00	–6.22 ± 0.02
ETH2AMM-2	–5.91 ± 0.02	–6.06 ± 0.02	0.15 ± 0.03	0.00	–6.08 ± 0.02
ETH2AMM-3d	–5.69 ± 0.02	–6.06 ± 0.02	0.37 ± 0.03	0.00	–6.08 ± 0.02
ACE2PEOL-2	1.02 ± 0.02	1.05 ± 0.03	–0.03 ± 0.04	0.11	1.03 ± 0.02
ACE2PEOL-3d	1.05 ± 0.02	1.05 ± 0.03	0.00 ± 0.04	1.00	1.03 ± 0.02

^aSee Table 2 for abbreviations used.

^bp-value obtained using Welch’ t test (cf. main text).

^cBest practice results from Table 4.

^dNaive approach.