TABLE II.

Computed ΔG^L→H values (in kcal/mol) and distribution overlap scores for a methyl diphosphate in water.^a

			ΔG					Overlap scores
Low	High	Constraints	M-λ TI	1-λ FEP	LRA	BAR	Staged	ΠLH	ΠHL	Overlap %	KHL	KLH
C36	DFTB3	Free	−18 857.3	−18 845.1	−18 858.2	…	−18 858.0	−3.92	−3.92	0.00	0.22	0.45
				(0.5)	(0.6)		(1.9)
C36	DFTB3	Frozen	…	−18 885.0	−18 885.9	−18 885.9	…	−2.00	−1.52	0.70	0.75	0.68
				(0.7)	(0.6)	…
MULL	DFTB3	B + A	…	−18 813.3	−18 814.9	−18 814.9	…	−0.22	0.88	2.11	0.77	0.93
				(0.3)	(0.3)	…
MULL	DFTB3	Frozen	…	−18 820.4	−18 820.3	−18 820.3	…	2.69	2.95	84.75	0.81	0.83
				(0.1)	(0.1)	…
DFTB3	B3LYP	Free	…	−765 491.4	−765 494.1	−765 493.8	…	−1.20	−1.63	0.17	0.33	0.02
				(0.3)	(0.3)	…
DFTB3	B3LYP	B + A	…	−765 501.7	−765 502.6	−765 502.3	…	0.66	0.09	5.36	0.80	0.90
				(0.2)	(0.2)	(0.2)

^aSee footnote of Table I for notations; B+A means constrained bond lengths and restrained bond angles with a force constant of 300 kcal/mol rad². For detailed data for the staged transformation with different X₀, ${\mathbf{X}}_0^{\prime }$ combinations, see Table IV.