Multi-Modal Molecular Representation Learning via Structure Awareness

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Rong Yin, Ruyue Liu, Xiaoshuai Hao, Xingrui Zhou, Yong Liu, Can Ma, Weiping Wang

Published: 2025, Last Modified: 21 Jan 2026IEEE Trans. Image Process. 2025EveryoneRevisionsBibTeXCC BY-SA 4.0
Abstract: Accurate extraction of molecular representations is a critical step in the drug discovery process. In recent years, significant progress has been made in molecular representation learning methods, among which multi-modal molecular representation methods based on images, and 2D/3D topologies have become increasingly mainstream. However, existing these multi-modal approaches often directly fuse information from different modalities, overlooking the potential of intermodal interactions and failing to adequately capture the complex higher-order relationships and invariant features between molecules. To overcome these challenges, we propose a structure-awareness-based multi-modal self-supervised molecular representation pre-training framework (MMSA) designed to enhance molecular graph representations by leveraging invariant knowledge between molecules. The framework consists of two main modules: the multi-modal molecular representation learning module and the structure-awareness module. The multi-modal molecular representation learning module collaboratively processes information from different modalities of the same molecule to overcome intermodal differences and generate a unified molecular embedding. Subsequently, the structure-awareness module enhances the molecular representation by constructing a hypergraph structure to model higher-order correlations between molecules. This module also introduces a memory mechanism for storing typical molecular representations, aligning them with memory anchors in the memory bank to integrate invariant knowledge, thereby improving the model’s generalization ability. Compared to existing multi-modal approaches, MMSA can be seamlessly integrated with any graph-based method and supports multiple molecular data modalities, ensuring both versatility and compatibility. Extensive experiments have demonstrated the effectiveness of MMSA, which achieves state-of-the-art performance on the MoleculeNet benchmark, with average ROC-AUC improvements ranging from 1.8% to 9.6% over baseline methods.