Generating stable molecules using imitation and reinforcement learning

• Published in: Machine learning: science and technology 2022-03, Vol.3 (1), p.15008
• Main Authors: Ager Meldgaard, Søren, Köhler, Jonas, Lund Mortensen, Henrik, Christiansen, Mads-Peter V, Noé, Frank, Hammer, Bjørk
• Format: Article
• Language: English
• Subjects: Cartesian coordinates; chemical physics; chemical space; Chemical synthesis; global optimization; Graph representations; Graphical representations; imitation learning; Isomers; Machine learning; Quantum chemistry; reinforcement learning; Stability; Stoichiometry; Training
• ISSN: 2632-2153; 2632-2153
• DOI: 10.1088/2632-2153/ac3eb4

Chemical space is routinely explored by machine learning methods to discover interesting molecules, before time-consuming experimental synthesizing is attempted. However, these methods often rely on a graph representation, ignoring 3D information necessary for determining the stability of the molecules. We propose a reinforcement learning (RL) approach for generating molecules in Cartesian coordinates allowing for quantum chemical prediction of the stability. To improve sample-efficiency we learn basic chemical rules from imitation learning (IL) on the GDB-11 database to create an initial model applicable for all stoichiometries. We then deploy multiple copies of the model conditioned on a specific stoichiometry in a RL setting. The models correctly identify low energy molecules in the database and produce novel isomers not found in the training set. Finally, we apply the model to larger molecules to show how RL further refines the IL model in domains far from the training data.