All workflows were implemented using the Icolos workflow manager . Workflows were specified as a series of sequentially executed steps using JSON configuration files. For full workflow configurations, we refer to the SI. This approach makes the setup straightforward, reproducible and transferable between different protein-ligand systems with only minimal changes required, whilst allowing for efficient parallelisation and utilization of HPC resources through the built-in Slurm interface. Icolos also enables error checking and failure handling for each job required to evaluate a typical ligand perturbation map.