First, we performed non-adaptive runs for all ligands using the same number of λ-windows for each stage as Alibay et al.. We allocated 5 ns per window with 1 ns discarded to equilibration, which reflects common practice in the literature. Reassuringly, the non-adaptive SOMD runs produced a very similar correlation with experiment compared to the GRO- and the experimental results were taken from Grädler et al., who used surface plasmon resonance. The experimental uncertainties were assumed to be 0.5 kcal mol -1 . A detailed breakdown of the components of the calculated binding free energies is given in Table .