To evaluate the success of the optimization, the predicted properties' distributions were compared (Figure ). After optimization for A 2A R affinity, a strong shift to higher predicted affinity (pKi) is achieved in the maximized model (µ 8.76, σ 0.51) compared to the fine-tuned model (µ 6.62, σ 0.86) (Figure ). A similar, although less pronounced shift is observed for the optimization of affinity in combination with the maximization/minimization of FU The plausibility of the generated molecules was assessed through visual inspection of a UMAP of the dataset and the generated molecules combined 5. The fine-tuned generators match the distribution of the dataset neatly (second row Figure ). The distribution of the molecules generated by reinforced generators matches the areas with the respective high/low property values in the dataset. Notably, the generated molecules cover different areas of the dataset depending on the optimization objectives. UMAPs for the single PK objective generators are available in the supplementary information (Supplementary Figure ).