As shown in Fig. , we see very good agreement between the calculated and experimental affinities, with a Pearson r of 0.89 ± 0.03, and a Kendall 𝜏 of 0.67 ± 0.05. However, we observe a RMSE of 2.75 ± 0.20 kcal/mol. As outlined in Fig. , each dataset deviates to varying degrees from experiment, with only PWWP1 showing an RMSE close to 1 kcal/mol. The correlation shown here is on par, if not better, than other comparable alchemical free energy studies . Whilst the RMSE is larger than the 1 kcal/mol limit shown by some other ABFE studies , similar system dependent shifts have been reported previously .