# RAG-Enhanced Collaborative LLM Agents for Drug Discovery

arXiv: https://arxiv.org/abs/2502.17506 · HTML: https://mlsanity.com/paper/2502.17506/

## Key facts

- Cited by 18 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 50 of its 81 references that are in the map.
- First posted on arXiv 22 Feb 2025.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 30 of 50)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer](https://mlsanity.com/paper/1910.10683/) (2019)
- [LLaMA: Open and Efficient Foundation Language Models](https://mlsanity.com/paper/2302.13971/) (2023)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Large Language Models are Zero-Shot Reasoners](https://mlsanity.com/paper/2205.11916/) (2022)
- [A Survey of Large Language Models](https://mlsanity.com/paper/2303.18223/) (2023)
- [A Survey on Large Language Model based Autonomous Agents](https://mlsanity.com/paper/2308.11432/) (2023)
- [Retrieval-Augmented Generation for Large Language Models: A Survey](https://mlsanity.com/paper/2312.10997/) (2023)
- [Survey of Hallucination in Natural Language Generation](https://mlsanity.com/paper/2202.03629/) (2022)
- [SciBERT: A Pretrained Language Model for Scientific Text](https://mlsanity.com/paper/1903.10676/) (2019)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Galactica: A Large Language Model for Science](https://mlsanity.com/paper/2211.09085/) (2022)
- [ChatEval: Towards Better LLM-based Evaluators through Multi-Agent Debate](https://mlsanity.com/paper/2308.07201/) (2023)
- [An Empirical Study of Catastrophic Forgetting in Large Language Models During Continual Fine-tuning](https://mlsanity.com/paper/2308.08747/) (2023)
- [Instruction Tuning for Large Language Models: A Survey](https://mlsanity.com/paper/2308.10792/) (2023)
- [Large Language Models: A Survey](https://mlsanity.com/paper/2402.06196/) (2024)
- [A Survey on RAG Meeting LLMs: Towards Retrieval-Augmented Large Language Models](https://mlsanity.com/paper/2405.06211/) (2024)
- [StructGPT: A General Framework for Large Language Model to Reason over Structured Data](https://mlsanity.com/paper/2305.09645/) (2023)
- [Pre-training Molecular Graph Representation with 3D Geometry](https://mlsanity.com/paper/2110.07728/) (2021)
- [Does Fine-Tuning LLMs on New Knowledge Encourage Hallucinations?](https://mlsanity.com/paper/2405.05904/) (2024)
- [SciMON: Scientific Inspiration Machines Optimized for Novelty](https://mlsanity.com/paper/2305.14259/) (2023)
- [Translation between Molecules and Natural Language](https://mlsanity.com/paper/2204.11817/) (2022)
- [Multi-modal Molecule Structure-text Model for Text-based Retrieval and Editing](https://mlsanity.com/paper/2212.10789/) (2022)
- [PaperQA: Retrieval-Augmented Generative Agent for Scientific Research](https://mlsanity.com/paper/2312.07559/) (2023)
- [Mol-Instructions: A Large-Scale Biomolecular Instruction Dataset for Large Language Models](https://mlsanity.com/paper/2306.08018/) (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)
- [Empowering Biomedical Discovery with AI Agents](https://mlsanity.com/paper/2404.02831/) (2024)
- [BioT5: Enriching Cross-modal Integration in Biology with Chemical Knowledge and Natural Language Associations](https://mlsanity.com/paper/2310.07276/) (2023)
- [A Review of Large Language Models and Autonomous Agents in Chemistry](https://mlsanity.com/paper/2407.01603/) (2024)

## Built on by (most cited first, 18 of 18)

- [A Survey of Context Engineering for Large Language Models](https://mlsanity.com/paper/2507.13334/) (2025)
- [From AI for Science to Agentic Science: A Survey on Autonomous Scientific Discovery](https://mlsanity.com/paper/2508.14111/) (2025)
- [A Survey of Agentic Reasoning for Large Language Models: Towards Recursively Self-Improving and Collective Agents](https://mlsanity.com/paper/2601.12538/) (2026)
- [Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics](https://mlsanity.com/paper/2510.09901/) (2025)
- [Chunk Twice, Embed Once: A Systematic Study of Segmentation and Representation Trade-offs in Chemistry-Aware Retrieval-Augmented Generation](https://mlsanity.com/paper/2506.17277/) (2025)
- [IR-Agent: Expert-Inspired LLM Agents for Structure Elucidation from Infrared Spectra](https://mlsanity.com/paper/2508.16112/) (2025)
- [Mozi: Governed Autonomy for Drug Discovery LLM Agents](https://mlsanity.com/paper/2603.03655/) (2026)
- [DrugMCTS: a drug repurposing framework combining multi-agent, RAG and Monte Carlo Tree Search](https://mlsanity.com/paper/2507.07426/) (2025)
- [Generative AI for Healthcare: Fundamentals, Challenges, and Perspectives](https://mlsanity.com/paper/2510.24551/) (2025)
- [Speak to a Protein: An Interactive Multimodal Co-Scientist](https://mlsanity.com/paper/2510.17826/) (2025)
- [Agentic AI in Healthcare & Medicine: A Seven-Dimensional Taxonomy for Empirical Evaluation of LLM-based Agents](https://mlsanity.com/paper/2602.04813/) (2026)
- [UrbanMind: Towards Urban General Intelligence via Tool-Enhanced Retrieval-Augmented Generation and Multilevel Optimization](https://mlsanity.com/paper/2507.04706/) (2025)
- [ADSeeker: A Knowledge-Grounded Reasoning Framework for Industry Anomaly Detection and Reasoning](https://mlsanity.com/paper/2508.03088/) (2025)
- [Valid Property-Enhanced Contrastive Learning for Targeted Optimization & Resampling for Novel Drug Design](https://mlsanity.com/paper/2509.00684/) (2025)
- [Evaluating Agentic Bioinformatics through Function, Evidence, and Validation](https://mlsanity.com/paper/2607.27556/) (2026)
- [QuantumMind: Constraint-Grounded Agentic Reasoning for Speedup Analysis in Quantum Computing](https://mlsanity.com/paper/2608.07743/) (2026)
- [Multi-Granular Rationale-Guided Molecular LLM for Property Prediction](https://mlsanity.com/paper/2608.10480/) (2026)
- [Molecular LLM Agents: From Architectural Design to Scientific Autonomy](https://mlsanity.com/paper/2608.23104/) (2026)

## Abstract (arXiv)

Recent advances in large language models (LLMs) have shown great potential to accelerate drug discovery. However, the specialized nature of biochemical data often necessitates costly domain-specific fine-tuning, posing major challenges. First, it hinders the application of more flexible general-purpose LLMs for cutting-edge drug discovery tasks. More importantly, it limits the rapid integration of the vast amounts of scientific data continuously generated through experiments and research. Compounding these challenges is the fact that real-world scientific questions are typically complex and open-ended, requiring reasoning beyond pattern matching or static knowledge retrieval.To address these challenges, we propose CLADD, a retrieval-augmented generation (RAG)-empowered agentic system tailored to drug discovery tasks. Through the collaboration of multiple LLM agents, CLADD dynamically retrieves information from biomedical knowledge bases, contextualizes query molecules, and integrates relevant evidence to generate responses - all without the need for domain-specific fine-tuning. Crucially, we tackle key obstacles in applying RAG workflows to biochemical data, including data heterogeneity, ambiguity, and multi-source integration. We demonstrate the flexibility and effectiveness of this framework across a variety of drug discovery tasks, showing that it outperforms general-purpose and domain-specific LLMs as well as traditional deep learning approaches. Our code is publicly available at https://github.com/Genentech/CLADD.