Curiosity as a Self-Supervised Method to Improve Exploration in De novo Drug Design

Currently, deep learning has advanced by leaps and bounds. However, the proposed techniques still lack an efficient exploration of the large chemical space. Most of these methods explore a small fragment of the chemical space of known drugs, if the desired molecules were not found, the process ends. In this work, we introduce a curiosity-driven method to force the model to navigate many parts of the chemical space, therefore, achieving higher desirability and diversity as well. At first, we train a recurrent neural network-based general molecular generator (G), then we fine-tune G to maximize curiosity and desirability. We define curiosity as the Tanimoto similarity between two generated molecules, a first molecule generated by G, and a second one generated by a copy of G (Gcopy). We only backpropagate the loss through G while keeping Gcopy unchanged. We benchmarked our approach against two desirable chemical properties related to drug-likeness and showed that the discovered chemical space can be significantly expanded, thus, discovering a higher number of desirable molecules with more diversity and potentially easier to synthesize.