Output from the perturbation mapping steps was parsed internally to a unified PerturbationMap data structure, capturing the node identity and graph connectivity, and subsequently driving the remainder of the workflow. The PMX calculation was then set up, involving construction of the output directory structure and generation of protein and ligand parameters. The protein was parametrised with gmx pdb2gmx using the AMBERff99sb*-ILDN forcefield . GROMACS version 2021.6 was used for all preprocessing and simulations. ACPYPE version 2022.1.3 and Antechamber version 21.0 programs were used to assign GAFF2 parameters and AM1-BCC partial charges for the ligands. pmx atomMapper was then run to establish a mapping between the atoms to be morphed between ligand pairs, followed by pmx ligandHybrid to generate the GROMACS topologies for hybrid molecules. Full systems were then assembled, and subsequently prepared for simulation using the step pmx box water ions. In this step, the standard GROMACS tools were used to place each system in a dodecahedral box with a buffer of at least 1.2 nm from solute to box edge, solvate with the TIP3P water model and neutralise with sodium and chloride ions at a concentration of 0.15 M.