# ProtTeX: Structure-In-Context Reasoning and Editing of Proteins with Large Language Models

arXiv: https://arxiv.org/abs/2503.08179 · HTML: https://mlsanity.com/paper/2503.08179/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 23 of its 65 references that are in the map.
- First posted on arXiv 11 Mar 2025.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)

## Builds on (most cited first, 23 of 23)

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [Llama 2: Open Foundation and Fine-Tuned Chat Models](https://mlsanity.com/paper/2307.09288/) (2023)
- [Scaling Laws for Neural Language Models](https://mlsanity.com/paper/2001.08361/) (2020)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [The Curious Case of Neural Text Degeneration](https://mlsanity.com/paper/1904.09751/) (2019)
- [A Survey of Large Language Models](https://mlsanity.com/paper/2303.18223/) (2023)
- [Emergent Abilities of Large Language Models](https://mlsanity.com/paper/2206.07682/) (2022)
- [OpenAI o1 System Card](https://mlsanity.com/paper/2412.16720/) (2024)
- [Chameleon: Mixed-Modal Early-Fusion Foundation Models](https://mlsanity.com/paper/2405.09818/) (2024)
- [Emu3: Next-Token Prediction is All You Need](https://mlsanity.com/paper/2409.18869/) (2024)
- [Multimodal Chain-of-Thought Reasoning in Language Models](https://mlsanity.com/paper/2302.00923/) (2023)
- [Continual Pre-training of Language Models](https://mlsanity.com/paper/2302.03241/) (2023)
- [Scaling Autoregressive Multi-Modal Models: Pretraining and Instruction Tuning](https://mlsanity.com/paper/2309.02591/) (2023)
- [Emu: Generative Pretraining in Multimodality](https://mlsanity.com/paper/2307.05222/) (2023)
- [Can We Generate Images with CoT? Let's Verify and Reinforce Image Generation Step by Step](https://mlsanity.com/paper/2501.13926/) (2025)
- [BioMedGPT: Open Multimodal Generative Pre-trained Transformer for BioMedicine](https://mlsanity.com/paper/2308.09442/) (2023)
- [Liquid: Language Models are Scalable and Unified Multi-modal Generators](https://mlsanity.com/paper/2412.04332/) (2024)
- [ProLLaMA: A Protein Large Language Model for Multi-Task Protein Language Processing](https://mlsanity.com/paper/2402.16445/) (2024)
- [ProtChatGPT: Towards Understanding Proteins with Large Language Models](https://mlsanity.com/paper/2402.09649/) (2024)
- [A Survey on LLM Inference-Time Self-Improvement](https://mlsanity.com/paper/2412.14352/) (2024)
- [Supervised Fine-tuning in turn Improves Visual Foundation Models](https://mlsanity.com/paper/2401.10222/) (2024)
- [TourSynbio: A Multi-Modal Large Model and Agent Framework to Bridge Text and Protein Sequences for Protein Engineering](https://mlsanity.com/paper/2408.15299/) (2024)

## Built on by (most cited first, 4 of 4)

- [Flow-Matching-Based Protein Structure Tokenizer Made Efficient and Easy](https://mlsanity.com/paper/2609.33129/) (2026)
- [Protein as a Second Language for LLMs](https://mlsanity.com/paper/2510.11188/) (2025)
- [BioBridge: Bridging Proteins and Language for Enhanced Biological Reasoning with LLMs](https://mlsanity.com/paper/2602.17680/) (2026)
- [MIMIC: A Generative Multimodal Foundation Model for Biomolecules](https://mlsanity.com/paper/2604.24506/) (2026)

## Abstract (arXiv)

Large language models have made remarkable progress in the field of molecular science, particularly in understanding and generating functional small molecules. This success is largely attributed to the effectiveness of molecular tokenization strategies. In protein science, the amino acid sequence serves as the sole tokenizer for LLMs. However, many fundamental challenges in protein science are inherently structure-dependent. The absence of structure-aware tokens significantly limits the capabilities of LLMs for comprehensive biomolecular comprehension and multimodal generation. To address these challenges, we introduce a novel framework, ProtTeX, which tokenizes the protein sequences, structures, and textual information into a unified discrete space. This innovative approach enables joint training of the LLM exclusively through the Next-Token Prediction paradigm, facilitating multimodal protein reasoning and generation. ProtTeX enables general LLMs to perceive and process protein structures through sequential text input, leverage structural information as intermediate reasoning components, and generate or manipulate structures via sequential text output. Experiments demonstrate that our model achieves significant improvements in protein function prediction, outperforming the state-of-the-art domain expert model with a twofold increase in accuracy. Our framework enables high-quality conformational generation and customizable protein design. For the first time, we demonstrate that by adopting the standard training and inference pipelines from the LLM domain, ProtTeX empowers decoder-only LLMs to effectively address diverse spectrum of protein-related tasks.