DrugMCTS: a drug repurposing framework combining multi-agent, RAG and Monte Carlo Tree Search

Abstract: Recent advances in LLMs have demonstrated considerable potential in scientific domains such as drug discovery. However, their effectiveness remains constrained when reasoning extends beyond the knowledge acquired during pretraining. Conventional approaches, such as fine-tuning or retrieval-augmented generation, face limitations in either imposing high computational overhead or failing to fully exploit structured scientific data. To overcome these challenges, we propose DrugMCTS, a novel framework that synergistically integrates RAG, multi-agent collaboration, and Monte Carlo Tree Search for drug repurposing. The framework employs five specialized agents tasked with retrieving and analyzing molecular and protein information, thereby enabling structured and iterative reasoning. Without requiring domain-specific fine-tuning, DrugMCTS empowers Qwen2.5-7B-Instruct to outperform Deepseek-R1 by over 20\%. Extensive experiments on the DrugBank and KIBA datasets demonstrate that DrugMCTS achieves substantially higher recall and robustness compared to both general-purpose LLMs and deep learning baselines. Our results highlight the importance of structured reasoning, agent-based collaboration, and feedback-driven search mechanisms in advancing LLM applications for drug discovery.