# Multi-Granular Rationale-Guided Molecular LLM for Property Prediction

arXiv: https://arxiv.org/abs/2608.10480 · HTML: https://mlsanity.com/paper/2608.10480/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 21 of its 49 references that are in the map.
- First posted on arXiv 11 Aug 2026.

## Builds on (most cited first, 21 of 21)

- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Finetuned Language Models Are Zero-Shot Learners](https://mlsanity.com/paper/2109.01652/) (2021)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [GNNExplainer: Generating Explanations for Graph Neural Networks](https://mlsanity.com/paper/1903.03894/) (2019)
- [On Explainability of Graph Neural Networks via Subgraph Explorations](https://mlsanity.com/paper/2102.05152/) (2021)
- [Pre-training Molecular Graph Representation with 3D Geometry](https://mlsanity.com/paper/2110.07728/) (2021)
- [Large-Scale Chemical Language Representations Capture Molecular Structure and Properties](https://mlsanity.com/paper/2106.09553/) (2021)
- [Motif-based Graph Self-Supervised Learning for Molecular Property Prediction](https://mlsanity.com/paper/2110.00987/) (2021)
- [MolCA: Molecular Graph-Language Modeling with Cross-Modal Projector and Uni-Modal Adapter](https://mlsanity.com/paper/2310.12798/) (2023)
- [LlaSMol: Advancing Large Language Models for Chemistry with a Large-Scale, Comprehensive, High-Quality Instruction Tuning Dataset](https://mlsanity.com/paper/2402.09391/) (2024)
- [Drug discovery with explainable artificial intelligence](https://mlsanity.com/paper/2007.00523/) (2020)
- [InstructMol: Multi-Modal Integration for Building a Versatile and Reliable Molecular Assistant in Drug Discovery](https://mlsanity.com/paper/2311.16208/) (2023)
- [GIT-Mol: A Multi-modal Large Language Model for Molecular Science with Graph, Image, and Text](https://mlsanity.com/paper/2308.06911/) (2023)
- [Towards 3D Molecule-Text Interpretation in Language Models](https://mlsanity.com/paper/2401.13923/) (2024)
- [nach0: Multimodal Natural and Chemical Languages Foundation Model](https://mlsanity.com/paper/2311.12410/) (2023)
- [LLaMo: Large Language Model-based Molecular Graph Assistant](https://mlsanity.com/paper/2411.00871/) (2024)
- [RAG-Enhanced Collaborative LLM Agents for Drug Discovery](https://mlsanity.com/paper/2502.17506/) (2025)
- [Mol-LLaMA: Towards General Understanding of Molecules in Large Molecular Language Model](https://mlsanity.com/paper/2502.13449/) (2025)
- [MolProphecy: Bridging Medicinal Chemists' Knowledge and Molecular Pre-Trained Models via a Multi-Modal Framework](https://mlsanity.com/paper/2507.02932/) (2025)

## Abstract (arXiv)

Large language models (LLMs) are widely applied across chemical tasks, such as molecular property prediction, which underpins drug discovery. Molecular LLMs represent a molecule through several modalities, notably a 1D SMILES sequence or a 2D molecular graph. Both encode molecular information implicitly, so the contribution of individual substructures remains opaque. Retrieval and augmentation methods add context, but from external sources. However, the cues chemists reason over are the internal substructures that drive a property up or down. We propose MR-MoL, a multi-granular rationale-guided molecular LLM that supplies this evidence directly. A fine-tuned GNN scores each substructure through masking, and the most influential ones are serialized as a ranked, direction-tagged rationale that the LLM reads alongside the SMILES sequence and molecular graph. The rationale spans three levels of granularity: Murcko scaffolds with their side chains, BRICS fragments, and functional groups. This is, to our knowledge, the first method to expose GNN-derived attributions to an LLM as evidence for property prediction. On eight MoleculeNet tasks, MR-MoL achieves the best overall results among generalist models and narrows the gap to specialist models tuned for each task. Five diagnostics further confirm that the model reads the rationale rather than merely benefiting from its presence. Its direction, rank, and substructure each shape the prediction, and its attributions reproduce known structure-property relationships.