Curiosity as a Self-Supervised Method to Improve Exploration in De novo Drug Design
This addresses a bottleneck in drug design for researchers by improving exploration, though it appears incremental as it builds on existing molecular generation techniques.
The paper tackles the problem of inefficient exploration in de novo drug design by introducing a curiosity-driven method that forces the model to navigate more of the chemical space, resulting in significantly expanded discovery of desirable molecules with higher diversity.
In recent years, deep learning has demonstrated promising results in de novo drug design. 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. All Code and data used in this paper are available at https://github.com/amine179/Curiosity-RL-for-Drug-Design.