Previous work using this data set of input transformations and target proteins has demonstrated that an ensemble of 5 replica simulations using 13 alchemical windows with 4 ns of sampling per window provides a good trade off of computation cost against accuracy and precision. For completeness we re-examine this rule of thumb in the context of our work's larger set of free energy estimators and MD engines. To perform this comparison 6 ligand transformations are selected from the full set of 54 named in previous work as l12-l35 and In figure we see a comparison of results collected using the long and large ensemble simulation protocols with one ligand transformation for the MCL1 target. What can be seen from the results in 9 is that even when using less production simulation the use of many independent and shorter simulations provides similar accuracy and better precision that using fewer and longer simulations. This is a repeated pattern: figure shows that the error on the large ensemble runs is much lower than that of the long runs when averaged over all 6 transformations examined here. Table compares the accuracy of large ensemble and long runs and shows that, indeed, averaged over all ligand transformations, the accuracy of these methods is similar despite using less overall simulation time in the large ensemble runs.