Guo, JeffSchwaller, Philippe2024-05-012024-05-012024-05-012024-04-1010.1021/jacsau.4c00066https://infoscience.epfl.ch/handle/20.500.14299/207662WOS:001200193000001Sample efficiency is a fundamental challenge in de novo molecular design. Ideally, molecular generative models should learn to satisfy a desired objective under minimal calls to oracles (computational property predictors). This problem becomes more apparent when using oracles that can provide increased predictive accuracy but impose significant computational cost. Consequently, designing molecules that are optimized for such oracles cannot be achieved under a practical computational budget. Molecular generative models based on simplified molecular-input line-entry system (SMILES) have shown remarkable sample efficiency when coupled with reinforcement learning, as demonstrated in the practical molecular optimization (PMO) benchmark. Here, we first show that experience replay drastically improves the performance of multiple previously proposed algorithms. Next, we propose a novel algorithm called Augmented Memory that combines data augmentation with experience replay. We show that scores obtained from oracle calls can be reused to update the model multiple times. We compare Augmented Memory to previously proposed algorithms and show significantly enhanced sample efficiency in an exploitation task, a drug discovery case study requiring both exploration and exploitation, and a materials design case study optimizing explicitly for quantum-mechanical properties. Our method achieves a new state-of-the-art in sample-efficient de novo molecular design, outperforming all of the previously reported methods. The code is available at https://github.com/schwallergroup/augmented_memory.Physical SciencesGenerative Molecular DesignSample EfficiencyDrug DiscoveryMaterials DesignReinforcementlearningtext::journal::journal article::research article