Since all BACE1 inhibitors in this study were positively charged, instead of running absolute hydration free energy calculations in the solvent leg of the thermodynamic cycle, we performed relative hydration free energy calculations using a similar SepTop approach as in the binding Correlation between calculated (NES Orion) and experimental binding free energies for 10 MALT1 inhibitors. Plot was generated using arsenic. The correlation and error statistics are worse than the ones obtained using SepTop (Figure ). A comparison between NES and SepTop values is shown in SI Figure .