The wall clock time required to produce a ∆∆G value for one transformation involving proteins of typical size (250-350 residues) is about 6-8 hours using CPUs and < 2 hours using a single GPU. We note that ensemble based workflows allow scale out on emerging exascale architectures so as to perform hundreds of ∆∆G calculations within the same wall clock time as required for a single calculation. We have been able to exploit the entirety of SuperMUC-NG (ca 310k cores) for such purposes several times in the past under so-called "block operations". All hybrid ligands were built automatically using TIES20. The TIES toolkit has already been released for open use and can be accessed at .