The graph-based genetic algorithm (GBGA) utilizes the crossover and mutation operations as implemented by Jensen . During a crossover operation, the graph of one of the ligands is cut at random points and recombined with a fragment of a molecular graph from another individual. The mutation operations act directly on the molecular graph, adding, changing or removing atom(-type) or connectivity. Newly generated ligands are considered valid if they contain at least one molecular pattern that is considered to be a potential coordination site for the ligand. These patterns are phosphines, amines, carbenes are carbonyls. When more than one potential coordination site is detected, all possible constitutional conformers of the ligand attached to a Pd-containing reference catalyst are generated and 25 conformers of each are embedded and optimized at the GFN2-xTB level of theory. The coordination site with the highest binding energy is then chosen as the coordination site for that ligand.