MolRAG: Unlocking the Power of Large Language Models for Molecular Property Prediction

AbstractRecent LLMs exhibit limited effectiveness on molecular property prediction task due to the semantic gap between molecular representations and natural language, as well as the lack of domain-specific knowledge. To address these challenges, we propose MolRAG, a Retrieval-Augmented Generation framework integrating Chain-of-Thought reasoning for molecular property prediction. MolRAG operates by retrieving structurally analogous molecules as contextual references to guide stepwise knowledge reasoning through chemical structure-property relationships. This dual mechanism synergizes molecular similarity analysis with structured inference, while generating human-interpretable rationales grounded in domain knowledge. Experimental results show MolRAG outperforms pre-trained LLMs on four datasets, and even matches supervised methods, achieving performance gains of 1.1%–45.7% over direct prediction approaches, demonstrating versatile effectiveness. Our code is available at https://github.com/AcaciaSin/MolRAG.