Molecular Hypergraph Grammar with Its Application to Molecular Optimization

Molecular optimization aims to discover novel molecules with desirable properties, and its two fundamental challenges are: (i) it is not trivial to generate valid molecules in a controllable way due to hard chemical constraints such as the valency conditions, and (ii) it is often costly to evaluate a property of a novel molecule, and therefore, the number of property evaluations is limited. These challenges are to some extent alleviated by a combination of a variational autoencoder (VAE) and Bayesian optimization (BO), where VAE converts a molecule into/from its latent continuous vector, and BO optimizes a latent continuous vector (and its corresponding molecule) within a limited number of property evaluations. While the most recent work, for the first time, achieved 100% validity, its architecture is rather complex due to auxiliary neural networks other than VAE, making it difficult to train. This paper presents a molecular hypergraph grammar variational autoencoder (MHG-VAE), which uses a single VAE to achieve 100% validity. Our idea is to develop a graph grammar encoding the hard chemical constraints, called molecular hypergraph grammar (MHG), which guides VAE to always generate valid molecules. We also present an algorithm to construct MHG from a set of molecules.