The Supporting Information for this work contains all individual results for relative binding free energy calculations performed as well as the input used to generate these results https: //zenodo.org/record/5767275#.YbCZEXX7SV4. The results provided in the SI come from the main TIES protocol (table S1-S6) and the long and large ensemble TIES protocols table . Additionally we present an equivalent version of figure 10 plotted using decorrelated data (figure ). We provide information on the long time simulations performed in this work with NAMD3 and highlight some statistically significant results we observe in figures S2-S3.