Huanran Meng
2026
Interleaved Tool-Call Reasoning for Protein Function Understanding
Chuanliu Fan | Zicheng Ma | Huanran Meng | Aijia Zhang | Wenjie Du | Jun Zhang | Ziqiang Cao | Guohong Fu
Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers)
Chuanliu Fan | Zicheng Ma | Huanran Meng | Aijia Zhang | Wenjie Du | Jun Zhang | Ziqiang Cao | Guohong Fu
Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers)
Recent advances in large language models (LLMs) have highlighted the effectiveness of chain-of-thought reasoning in symbolic domains such as mathematics and programming. However, our study shows that directly transferring such text-based reasoning paradigms to protein function understanding is ineffective: reinforcement learning mainly amplifies superficial keyword patterns while failing to introduce new biological knowledge, resulting in limited generalization. We argue that protein function prediction is a knowledge-intensive scientific task that fundamentally relies on external biological priors and computational tools rather than purely internal reasoning. To address this gap, we propose Protein Function Understanding Agent (PFUA), a tool-augmented protein reasoning agent that unifies problem decomposition, tool invocation, and grounded answer generation. Instead of relying on long unconstrained reasoning traces, PFUA integrates domain-specific tools to produce verifiable intermediate evidence. Experiments on four benchmarks demonstrate that PFUA consistently outperforms text-only reasoning models with an average performance improvement of 103%. We believe PFUA has the potential to become a standard paradigm for agentic reasoning in knowledge-intensive life science domains.