Recalculating all free energies with the "optimised" adaptive protocol produced extremely similar results to the non-adaptive protocol (Figure and Table ) with good correlation with experiment, albeit for a small set of ligands. There was no significant evidence at 95 % confidence for differences in either the uncertainty between the adaptive and non-adaptive runs, nor the unsigned error compared to experiment (p = 0.36 in both cases using the Wilcoxon ranked-sign test). A relatively large amount of simulation time was allocated to these calculations using the same parameters as for the initial test systems, because the bound systems were relatively small and inexpensive (around half the cost of the MIF bound system). However, the adaptive protocol was still around 1.5 times cheaper than the non-adaptive protocol, and around 6 times cheaper than the protocol of Alibay et al..