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

Recent 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 structureproperty relationships.This dual mechanism synergizes molecular similarity analysis with structured inference, while generating humaninterpretable rationales grounded in domain knowledge.Experimental results show Mol-RAG 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.* Molecule 1: No 3D structure, no sulfone group, no aromatic ring * Molecule 2: Sulfone group, aromatic ring, but no 3D structure * Molecule 3: Sulfone group, aromatic ring, 3D structure, but no nitrogen-containing ring * Molecule 4: No sulfone group, aromatic ring, no 3D structure Now, let's analyze the question input molecule: O=SThis molecule has: * A sulfone group (S(=O)(=O)O) * An aromatic ring (c1cc2...) * A 3D structure (with a nitrogen-containing ring) * A sulfone group interacting with the nitrogen-containing ring Comparing the question input molecule to the examples, I notice that it has a sulfone group, an aromatic ring, and a 3D structure, which are similar to Molecule 3.However, the question input molecule has a nitrogen-containing ring, which is not present in Molecule 3. * Has fluorine atoms (C(F)(F)F) which may affect its properties.* Score: 0.6575, Label: No Example 2: * Has a different structure, with a carbonyl group (C(=O)CC(c2ccccc2)) and a sulfonamide group (Sc2ccccc21).* Score: 0.5634, Label: No Example 3: * Has a different structure, with a carbonyl group (C(=O)c2cc3ccccc3cc21) and no sulfonamide group.* Score: 0.5397, Label: No Example 4: * Has a different structure, with a hydroxyl group (O) and a bromine atom (Br), but no sulfonamide group.* Score: 0.5312, Label: No Now, let's analyze the input molecule: * It has a sulfonamide group (Sc2c1ccc1ccccc21) and a carbonyl group (CC(=O)N1c2ccccc2).* It has no fluorine atoms, unlike Example 1. * It has a relatively simple structure with a single aromatic ring and a sulfonamide group.