Active Learning Enables Extrapolation in Molecular Generative Models

Although generative models hold promise for discovering molecules with optimized desired properties, they often fail to suggest synthesizable molecules that improve upon the known molecules seen in training. We find that a key limitation is not in the molecule generation process itself, but in the poor generalization capabilities of molecular property predictors. We tackle this challenge by creating an active-learning, closed-loop molecule generation pipeline, whereby molecular generative models are iteratively refined on feedback from quantum chemical simulations to improve generalization to new chemical space. Compared against other generative model approaches, only our active learning approach generates molecules with properties that extrapolate beyond the training data (reaching up to 0.44 standard deviations beyond the training data range) and out-of-distribution molecule classification accuracy is improved by 79%. By conditioning molecular generation on thermodynamic stability data from the active-learning loop, the proportion of stable molecules generated is 3.5x higher than the next-best model.

Representing Polymers as Periodic Graphs with Learned Descriptors for Accurate Polymer Property Predictions

One of the grand challenges of utilizing machine learning for the discovery of innovative new polymers lies in the difficulty of accurately representing the complex structures of polymeric materials. Although a wide array of hand-designed polymer representations have been explored, there has yet to be an ideal solution for how to capture the periodicity of polymer structures, and how to develop polymer descriptors without the need for human feature design. In this work, we tackle these problems through the development of our periodic polymer graph representation. Our pipeline for polymer property predictions is comprised of our polymer graph representation that naturally accounts for the periodicity of polymers, followed by a message-passing neural network (MPNN) that leverages the power of graph deep learning to automatically learn chemically-relevant polymer descriptors. Across a diverse dataset of 10 polymer properties, we find that this polymer graph representation consistently outperforms hand-designed representations with a 20% average reduction in prediction error. Our results illustrate how the incorporation of chemical intuition through directly encoding periodicity into our polymer graph representation leads to a considerable improvement in the accuracy and reliability of polymer property predictions. We also demonstrate how combining polymer graph representations with message-passing neural network architectures can automatically extract meaningful polymer features that are consistent with human intuition, while outperforming human-derived features. This work highlights the advancement in predictive capability that is possible if using chemical descriptors that are specifically optimized for capturing the unique chemical structure of polymers.