Explainable prediction of catalysing enzymes from reactions using multilayer perceptrons

Abstract

Assigning or proposing a catalysing enzyme given a chemical or biochemical reaction is of great interest to life sciences and chemistry alike. The exploration and design of metabolic pathways or the challenge of finding more sustainable enzyme-catalysed alternatives to traditional organic reactions are just two examples of tasks that require an association between reaction and enzyme. However, given the lack of large and balanced annotated data sets of enzyme-catalysed reactions, assigning an enzyme to a reaction still relies on expert-curated rules and databases. Here, we present a data-driven explainable human-in-the-loop machine learning approach to support and ultimately automate the association of a catalysing enzyme with a given biochemical reaction. In addition, the proposed method is capable of predicting enzymes as candidate catalysts for arbitrary organic reactions. Finally, the introduced explainability and visualisation methods can easily be generalised to support other machine-learning approaches involving chemical and biochemical reactions.