TABLE IV.

Computed ΔG^L→H values (in kcal/mol) for a fully unrestrained methyl diphosphate in solution from the staged transformation approach using different combinations of confined reference structures (i.e., X₀, ${\mathbf{X}}_0^{\prime }$).^a

	${\mathbf{X}}_0^{\prime }$ sample 1	${\mathbf{X}}_0^{\prime }$ sample 2	${\mathbf{X}}_0^{\prime }$ sample 3	${\mathbf{X}}_0^{\prime }$ sample 4	${\mathbf{X}}_0^{\prime }$ sample 5
$\mathrm{\Delta }{G}_0^{L\to H}$	−18 878.6 ± 0.3	−18 878.6 ± 0.2	−18 876.4 ± 0.2	−18 872.8 ± 0.2	−18 880.5 ± 0.3
X0 sample 1	23.7/−18 854.8	21.6/−18 857.0	17.7/−18 858.7	16.0/−18 856.8	24.7/−18 855.8
X0 sample 2	22.9/−18 855.7	20.8/−18 857.8	16.9/−18 859.5	15.2/−18 857.6	23.9/−18 856.6
X0 sample 3	20.0/−18 858.6	17.8/−18 860.7	13.9/−18 862.4	12.3/−18 860.5	20.9/−18 859.6
X0 sample 4	23.2/−18 855.3	21.1/−18 857.5	17.2/−18 859.1	15.5/−18 857.2	24.2/−18 856.3
X0 sample 5	21.7/−18 856.9	19.6/−18 859.0	15.7/−18 860.7b	14.0/−18 858.8b	22.6/−18 857.8
Avg.	−18 858.0 ± 1.9

^aSee footnote a of Table III for the format of the entries. The average ΔG^L→H value is reported as the “Stage” entry in Table II.

^bFor these specific combinations, the confined structures (X₀, ${\mathbf{X}}_0^{\prime }$) are close to the minima on the L/H free energy surface based on the 2D projection [see Figs. 10(e) and 10(f)].