Enhancing property and activity prediction and interpretation using multiple molecular graph representations with...

Graph Neural Networks (GNNs) excel in compound property and activity prediction, but the choice of molecular graph representations significantly influences model learning and interpretation. While atom-level molecular graphs resemble natural topology, they overlook key substructures or functional groups and their interpretation partially aligns with chemical intuition. Recent research suggests alternative representations using reduced molecular graphs to integrate higher-level chemical information and leverages both representations for model. However, there is a lack of studies about applicability and impact of different molecular graphs on model learning and interpretation. Here, we introduce MMGX (Multiple Molecular Graph eXplainable discovery), investigating the effects of multiple molecular graphs, including Atom, Pharmacophore, JunctionTree, and FunctionalGroup, on model learning and interpretation with various perspectives. Our findings indicate that multiple graphs relatively improve model performance, but in varying degrees depending on datasets. Interpretation from multiple graphs in different views provides more comprehensive features and potential substructures consistent with background knowledge. These results help to understand model decisions and offer valuable insights for subsequent tasks. The concept of multiple molecular graph representations and diverse interpretation perspectives has broad applicability across tasks, architectures, and explanation techniques, enhancing model learning and interpretation for relevant applications in drug discovery.