The following simulations were all conducted with the OpenFE release 0.10.1 and the contained OpenFE CLI tools directly enabling the usage of the OpenFE-Relative Free Energy (RFE) protocol. OpenFE used for the simulations and the preparations OpenMM 8.0.0 76 using the GPU code, OpenMMTools, and OpenFFTools 0.13.0. The systems, except the vacuum systems, were first solvated using TIP3P waters up to a distance of 1.2 nm from the solute, directly defining the cubic periodic simulation box.