In this experiment, we perform a single property optimization, while constraining the explorable chemical space using a defined molecular scaffold that needs to be present in the generated molecules. This task is more closely related to a real drug-development process, as it mimics a typical lead optimization task. We base our experiment on a lead optimization paper by Stamford et al. in which an iminopyrimidine lead series was optimized for BACE1 inhibition . In order to evaluate whether our method can optimize for biological activity while constraining the explorable chemical space, we start the optimization from the same initial compound as in (Figure ). We fix the iminopyrimidinone scaffold (Figure ) by penalizing generated compounds that do not contain this substructure in the objective function. For the prediction of BACE1 activity we retrain the BACE1 model from the previous section, excluding all compounds with an iminopyrimidinone scaffold.