Figure shows the SHAP analysis applied to the GBR model using RDKit descriptors. Although the plot shows clearly how low or high values of each feature affect the models' prediction, some of these features (for example min energy state index ligand, Chi1v ligand, min absolute energy state index ligand) are not interpretable to scientist, which prevents human design in further chiral ligand optimization. Similar effects occur in the RFR model using RDKit features, shown in Figure . For this model, more features were used, but there is still a lack of chemical interpretability, as the case of Min and Max Energy State Index, Chi0n, and BertzCT (all describing the ligand). Although in both these models there are variables that are human interpretable, these consist of fragment counts in the substrate, which is not useful as usually the substrate to convert is not a variable of the reaction, where ligand optimization is the pre-eminent goal.