GDMol: Generative Double‐Masking Self‐Supervised Learning for Molecular Property Prediction

Abstract Background : Effective molecular feature representation is crucial for drug property prediction. Recent years have seen increased attention on graph neural networks (GNNs) that are pre‐trained using self‐supervised learning techniques, aiming to overcome the scarcity of labeled data in molecular property prediction. Traditional GNNs in self‐supervised molecular property prediction typically perform a single masking operation on the nodes and edges of the input molecular graph, masking only local information and insufficient for thorough self‐supervised training. Method : Hence, we propose a model for molecular property prediction based on generative double‐masking self‐supervised learning, termed as GDMol. This integrates generative learning into the self‐supervised learning framework for latent representation, and applies a second round of masking to these latent representations, enabling the model to better capture global information and semantic knowledge of the molecules for a richer, more informative representation, thereby achieving more accurate and robust molecular property prediction. Results : Our experiments on 5 datasets demonstrated superior performance of GDMol in predicting molecular properties across different domains. Moreover, we used the masking operation to traverse through the gradient changes of each node, the magnitude and sign of which reflect the positive and negative contribution respectively of the local structure in the molecule to the prediction outcome. This in‐depth interpretative analysis not only enhances the model's interpretability, but also provides more targeted insights and direction for optimizing drug molecules. Conclusions : In summary, this research offers novel insights on improving molecular property prediction tasks, and paves the way for further research on the application of generative learning and self‐supervised learning in the field of chemistry.