# Protein as a Second Language for LLMs

arXiv: https://arxiv.org/abs/2510.11188 · HTML: https://mlsanity.com/paper/2510.11188/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 22 of its 57 references that are in the map.
- First posted on arXiv 13 Oct 2025.

## Builds on (most cited first, 22 of 22)

- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Overcoming catastrophic forgetting in neural networks](https://mlsanity.com/paper/1612.00796/) (2016)
- [Galactica: A Large Language Model for Science](https://mlsanity.com/paper/2211.09085/) (2022)
- [ProGen2: Exploring the Boundaries of Protein Language Models](https://mlsanity.com/paper/2206.13517/) (2022)
- [Mol-Instructions: A Large-Scale Biomolecular Instruction Dataset for Large Language Models](https://mlsanity.com/paper/2306.08018/) (2023)
- [BioT5: Enriching Cross-modal Integration in Biology with Chemical Knowledge and Natural Language Associations](https://mlsanity.com/paper/2310.07276/) (2023)
- [ProtST: Multi-Modality Learning of Protein Sequences and Biomedical Texts](https://mlsanity.com/paper/2301.12040/) (2023)
- [OntoProtein: Protein Pretraining With Gene Ontology Embedding](https://mlsanity.com/paper/2201.11147/) (2022)
- [ProLLaMA: A Protein Large Language Model for Multi-Task Protein Language Processing](https://mlsanity.com/paper/2402.16445/) (2024)
- [xTrimoPGLM: Unified 100B-Scale Pre-trained Transformer for Deciphering the Language of Protein](https://mlsanity.com/paper/2401.06199/) (2024)
- [Prot2Text: Multimodal Protein's Function Generation with GNNs and Transformers](https://mlsanity.com/paper/2307.14367/) (2023)
- [ProtT3: Protein-to-Text Generation for Text-based Protein Understanding](https://mlsanity.com/paper/2405.12564/) (2024)
- [ProteinGPT: Multimodal LLM for Protein Property Prediction and Structure Understanding](https://mlsanity.com/paper/2408.11363/) (2024)
- [ProtLLM: An Interleaved Protein-Language LLM with Protein-as-Word Pre-Training](https://mlsanity.com/paper/2403.07920/) (2024)
- [A Fine-tuning Dataset and Benchmark for Large Language Models for Protein Understanding](https://mlsanity.com/paper/2406.05540/) (2024)
- [ProtChatGPT: Towards Understanding Proteins with Large Language Models](https://mlsanity.com/paper/2402.09649/) (2024)
- [Protein Large Language Models: A Comprehensive Survey](https://mlsanity.com/paper/2502.17504/) (2025)
- [EvoLlama: Enhancing LLMs' Understanding of Proteins via Multimodal Structure and Sequence Representations](https://mlsanity.com/paper/2412.11618/) (2024)
- [VenusX: Unlocking Fine-Grained Functional Understanding of Proteins](https://mlsanity.com/paper/2505.11812/) (2025)
- [Unifying Sequences, Structures, and Descriptions for Any-to-Any Protein Generation with the Large Multimodal Model HelixProtX](https://mlsanity.com/paper/2407.09274/) (2024)
- [ProtTeX: Structure-In-Context Reasoning and Editing of Proteins with Large Language Models](https://mlsanity.com/paper/2503.08179/) (2025)
- [Rethinking Text-based Protein Understanding: Retrieval or LLM?](https://mlsanity.com/paper/2505.20354/) (2025)

## Abstract (arXiv)

Deciphering the function of unseen protein sequences is a fundamental challenge with broad scientific impact, yet most existing methods depend on task-specific adapters or large-scale supervised fine-tuning. We introduce the "Protein-as-Second-Language" framework, which reformulates amino-acid sequences as sentences in a novel symbolic language that large language models can interpret through contextual exemplars. Our approach adaptively constructs sequence-question-answer triples that reveal functional cues in a zero-shot setting, without any further training. To support this process, we curate a bilingual corpus of 79,926 protein-QA instances spanning attribute prediction, descriptive understanding, and extended reasoning. Empirically, our method delivers consistent gains across diverse open-source LLMs and GPT-4, achieving up to 17.2% ROUGE-L improvement (average +7%) and even surpassing fine-tuned protein-specific language models. These results highlight that generic LLMs, when guided with protein-as-language cues, can outperform domain-specialized models, offering a scalable pathway for protein understanding in foundation models.