# Structure-Enhanced Protein Instruction Tuning: Towards General-Purpose Protein Understanding with LLMs

arXiv: https://arxiv.org/abs/2410.03553 · HTML: https://mlsanity.com/paper/2410.03553/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Builds on 54 of its 123 references that are in the map.
- First posted on arXiv 4 Oct 2024.

## Builds on (most cited first, 30 of 54)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer](https://mlsanity.com/paper/1910.10683/) (2019)
- [Visual Instruction Tuning](https://mlsanity.com/paper/2304.08485/) (2023)
- [Scaling Laws for Neural Language Models](https://mlsanity.com/paper/2001.08361/) (2020)
- [BLIP-2: Bootstrapping Language-Image Pre-training with Frozen Image Encoders and Large Language Models](https://mlsanity.com/paper/2301.12597/) (2023)
- [BERTScore: Evaluating Text Generation with BERT](https://mlsanity.com/paper/1904.09675/) (2019)
- [Flamingo: a Visual Language Model for Few-Shot Learning](https://mlsanity.com/paper/2204.14198/) (2022)
- [Sequence to Sequence Learning with Neural Networks](https://mlsanity.com/paper/1409.3215/) (2014)
- [A Comprehensive Survey on Graph Neural Networks](https://mlsanity.com/paper/1901.00596/) (2019)
- [InstructBLIP: Towards General-purpose Vision-Language Models with Instruction Tuning](https://mlsanity.com/paper/2305.06500/) (2023)
- [XLNet: Generalized Autoregressive Pretraining for Language Understanding](https://mlsanity.com/paper/1906.08237/) (2019)
- [ALBERT: A Lite BERT for Self-supervised Learning of Language Representations](https://mlsanity.com/paper/1909.11942/) (2019)
- [A Survey of Large Language Models](https://mlsanity.com/paper/2303.18223/) (2023)
- [Qwen-VL: A Versatile Vision-Language Model for Understanding, Localization, Text Reading, and Beyond](https://mlsanity.com/paper/2308.12966/) (2023)
- [PaLM-E: An Embodied Multimodal Language Model](https://mlsanity.com/paper/2303.03378/) (2023)
- [Transformer-XL: Attentive Language Models Beyond a Fixed-Length Context](https://mlsanity.com/paper/1901.02860/) (2019)
- [GShard: Scaling Giant Models with Conditional Computation and Automatic Sharding](https://mlsanity.com/paper/2006.16668/) (2020)
- [Align before Fuse: Vision and Language Representation Learning with Momentum Distillation](https://mlsanity.com/paper/2107.07651/) (2021)
- [mPLUG-Owl: Modularization Empowers Large Language Models with Multimodality](https://mlsanity.com/paper/2304.14178/) (2023)
- [Domain-Specific Language Model Pretraining for Biomedical Natural Language Processing](https://mlsanity.com/paper/2007.15779/) (2020)
- [A Survey on Multimodal Large Language Models](https://mlsanity.com/paper/2306.13549/) (2023)
- [Galactica: A Large Language Model for Science](https://mlsanity.com/paper/2211.09085/) (2022)
- [CogVLM: Visual Expert for Pretrained Language Models](https://mlsanity.com/paper/2311.03079/) (2023)
- [SimVLM: Simple Visual Language Model Pretraining with Weak Supervision](https://mlsanity.com/paper/2108.10904/) (2021)
- [TinyLlama: An Open-Source Small Language Model](https://mlsanity.com/paper/2401.02385/) (2024)
- [SE(3)-Transformers: 3D Roto-Translation Equivariant Attention Networks](https://mlsanity.com/paper/2006.10503/) (2020)

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

- [TokenSelect: Efficient Long-Context Inference and Length Extrapolation for LLMs via Dynamic Token-Level KV Cache Selection](https://mlsanity.com/paper/2411.02886/) (2024)
- [Graph is a Substrate Across Data Modalities](https://mlsanity.com/paper/2601.22384/) (2026)
- [Aligning Large Language Models with Searcher Preferences](https://mlsanity.com/paper/2603.10473/) (2026)
- [Patient-specific Biomolecular Instruction Tuning](https://mlsanity.com/paper/2509.22853/) (2025)

## Abstract (arXiv)

Proteins, as essential biomolecules, play a central role in biological processes, including metabolic reactions and DNA replication. Accurate prediction of their properties and functions is crucial in biological applications. Recent development of protein language models (pLMs) with supervised fine tuning provides a promising solution to this problem. However, the fine-tuned model is tailored for particular downstream prediction task, and achieving general-purpose protein understanding remains a challenge. In this paper, we introduce Structure-Enhanced Protein Instruction Tuning (SEPIT) framework to bridge this gap. Our approach incorporates a novel structure-aware module into pLMs to enrich their structural knowledge, and subsequently integrates these enhanced pLMs with large language models (LLMs) to advance protein understanding. In this framework, we propose a novel instruction tuning pipeline. First, we warm up the enhanced pLMs using contrastive learning and structure denoising. Then, caption-based instructions are used to establish a basic understanding of proteins. Finally, we refine this understanding by employing a mixture of experts (MoEs) to capture more complex properties and functional information with the same number of activated parameters. Moreover, we construct the largest and most comprehensive protein instruction dataset to date, which allows us to train and evaluate the general-purpose protein understanding model. Extensive experiments on both open-ended generation and closed-set answer tasks demonstrate the superior performance of SEPIT over both closed-source general LLMs and open-source LLMs trained with protein knowledge.