MolBridge: Atom-Level Joint Graph Refinement for Robust Drug-Drug Interaction Event Prediction

TL;DR

MolBridge is a novel atom-level joint graph refinement framework that improves drug-drug interaction event prediction by explicitly modeling atomic structures and inter-drug relationships, enhancing robustness and interpretability.

Contribution

Introduces MolBridge, a joint graph refinement method with a structure consistency module for better atom-level interaction modeling in DDI prediction.

Findings

Outperforms state-of-the-art baselines on benchmark datasets.

Achieves superior performance in long-tail and inductive scenarios.

Provides robust and interpretable DDI predictions across diverse molecular complexities.

Abstract

Drug combinations offer therapeutic benefits but also carry the risk of adverse drug-drug interactions (DDIs), especially under complex molecular structures. Accurate DDI event prediction requires capturing fine-grained inter-drug relationships, which are critical for modeling metabolic mechanisms such as enzyme-mediated competition. However, existing approaches typically rely on isolated drug representations and fail to explicitly model atom-level cross-molecular interactions, limiting their effectiveness across diverse molecular complexities and DDI type distributions. To address these limitations, we propose MolBridge, a novel atom-level joint graph refinement framework for robust DDI event prediction. MolBridge constructs a joint graph that integrates atomic structures of drug pairs, enabling direct modeling of inter-drug associations. A central challenge in such joint graph settings is the potential loss of information caused by over-smoothing when modeling long-range atomic dependencies. To overcome this, we introduce a structure consistency module that iteratively refines node features while preserving the global structural context. This joint design allows MolBridge to effectively learn both local and global interaction outperforms state-of-the-art baselines, achieving superior performance across long-tail and inductive scenarios. patterns, yielding robust representations across both frequent and rare DDI types. Extensive experiments on two benchmark datasets show that MolBridge consistently. These results demonstrate the advantages of fine-grained graph refinement in improving the accuracy, robustness, and mechanistic interpretability of DDI event prediction.This work contributes to Web Mining and Content Analysis by developing graph-based methods for mining and analyzing drug-drug interaction networks.