Table 2.

Data to calculate the free energy difference (ΔG_1,A→B) between the closed and open states of β-cyclodextrin in water by connecting the free energy surface in vacuum to that in water with both free energy calculations and endpoint methods. The times required to compute ΔG_0,A→B, $kT\text{ ln }(P_{0,a_1}^A/P_{1,a_1}^A)$, and $kT\text{ ln }(P_{0,b_1}^B/P_{1,b_1}^B)$ were significantly smaller than the times required to compute ΔG_1,A→B, ΔG_0→1,a1, and ΔG_0→1,b1, as can be seen by observing the small sizes of the error bars on the first set of quantities. The time required to compute ΔG_1,A→B was therefore dominated by the calculations of ΔG_0→1,a1 and ΔG_0→1,b1. The values for ΔG_0,A→B, $kT\text{ ln }(P_{0,a_1}^A/P_{1,a_1}^A)$, and $kT\text{ ln }(P_{0,b_1}^B/P_{1,b_1}^B)$ are common between TI and the endpoint method. The computation time for each of ΔG_0→1,a1 and ΔG_0→1,b1 in the endpoint method corresponds to that for a single λ for TI.

	Equation 1	Equation 2 TI	Equation 2 free energy functional/end point methods
ΔG1,A→B	1.0±0.1	1.0±0.8	1.2±0.2
ΔG0,A→B		3.12874 ±0.00007
$kT\text{ ln }(P_{0,a_1}^A/P_{1,a_1}^A)$		−0.393±0.002
ΔG0→1,a1		−56.4±0.3	−46.6±0.1
$kT\text{ ln }(P_{0,b_1}^B/P_{1,b_1}^B)$		−0.35±0.01
ΔG0→1,b1		−58.5±0.5	−48.5±0.1
Simulation time (ns)	~200	~200	~8