Constrained Molecule Generation Modelled Using the Grammar Constraint

Abstract Drug discovery is a very time-consuming and costly endeavour due to its huge design space and to the lengthy and failure-fraught process of bringing a product to market. Automating the generation of candidate molecules exhibiting some of the desired properties can help. Among the standard formats to encode molecules, SMILES is a widespread string representation. We propose a constraint programming model showcasing the grammar constraint to express the design space of organic molecules using the SMILES notation. We show how some common physicochemical properties --- such as molecular weight and lipophilicity --- and structural features can be expressed as constraints in the model. We also contribute a weighted counting algorithm for the grammar constraint, allowing us to use a belief propagation heuristic to guide the generation. Our experiments indicate that such a heuristic is key to driving the search towards desired molecules.