Whilst the outlined FE calculation methods facilitate scaling to large sets of compounds, the requirement for significant investment of expert time to manually set up, execute and evaluate such calculations remains a limitation to wider adoption, particularly outside of industrial research where access to commercial packages is more limited. To address this, we report the development of a fully automated end-to-end workflow employing constrained embedding and docking steps to facilitate non-equilibrium simulation (NES) based RBFE calculations starting from SMILES string ligand representations. The workflows are implemented using Icolos, our in-house, open-source workflow manager, which streamlines the configuration of complex, multi-step physics-based workflows and allows for flexible combination of commercial and open-source tools at various stages of the workflow .