During the attach phase, three restraints were applied to the guest molecule; two for the translation ( and ) and one for the orientation ( ). We only restrain the polar angle of the guest orientation because the host molecules of interest are cylindrically symmetrical. The restraint free energy was obtained by scaling the force constants from zero to one in 15 windows. The free energy of releasing the guest restraints in the unbound state was calculated semi-analytically, which includes the standard-state correction at 1 M. The force constants used for the host static restraints and the guest orientational restraints were: (a) distance restraints = 10.0 ∕ ∕Å 2 ; (b) angle and torsional restraints = 100 ∕ ∕ 2 .