MolExplain: An Interactive Tool for Explainable Molecular Property Prediction

Abstract

The application of machine learning to molecular property prediction has become increasingly prevalent in drug discovery, yet most models operate as black boxes, returning a prediction without revealing which structural features drive it. MolExplain addresses this gap by combining property prediction with sub-structure level visual explainability in an interactive web interface. The system featurizes molecules as Morgan fingerprints, classifies them using a trained XGBoost model, and applies SHAP attribution to produce a smooth heatmap overlay indicating which regions of the molecule contribute for or against the predicted property. Applied to cyclic peptide membrane permeability, the tool's attribution independently recovers the known role of backbone N-methylation in improving passive membrane diffusion, consistent with established chemistry. While demonstrated on cyclic peptides, the framework is designed to generalize to other molecular properties, positioning MolExplain as a platform for interactive, explainability-driven molecular design.