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Considering the significance of proteins, computational protein science has always been a critical scientific field, dedicated to revealing knowledge and developing applications within the protein sequence-structure-function paradigm. In…

Computational Engineering, Finance, and Science · Computer Science 2025-01-28 Wenqi Fan , Yi Zhou , Shijie Wang , Yuyao Yan , Hui Liu , Qian Zhao , Le Song , Qing Li

In this work we introduce RITA: a suite of autoregressive generative models for protein sequences, with up to 1.2 billion parameters, trained on over 280 million protein sequences belonging to the UniRef-100 database. Such generative models…

Quantitative Methods · Quantitative Biology 2022-07-18 Daniel Hesslow , Niccoló Zanichelli , Pascal Notin , Iacopo Poli , Debora Marks

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

In recent years, protein-text models have gained significant attention for their potential in protein generation and understanding. Current approaches focus on integrating protein-related knowledge into large language models through…

Computation and Language · Computer Science 2025-11-11 Juntong Wu , Zijing Liu , He Cao , Hao Li , Bin Feng , Zishan Shu , Ke Yu , Li Yuan , Yu Li

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses…

Machine Learning · Computer Science 2022-05-30 Pascal Notin , Mafalda Dias , Jonathan Frazer , Javier Marchena-Hurtado , Aidan Gomez , Debora S. Marks , Yarin Gal

Protein activity is a significant characteristic for recombinant proteins which can be used as biocatalysts. High activity of proteins reduces the cost of biocatalysts. A model that can predict protein activity from amino acid sequence is…

Quantitative Methods · Quantitative Biology 2018-07-23 X. Han , X. Wang , K. Zhou

At the intersection of the rapidly growing biological data landscape and advancements in Natural Language Processing (NLP), protein language models (PLMs) have emerged as a transformative force in modern research. These models have achieved…

Biomolecules · Quantitative Biology 2025-02-12 Lei Wang , Xudong Li , Han Zhang , Jinyi Wang , Dingkang Jiang , Zhidong Xue , Yan Wang

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based…

Many applications of machine learning methods involve an iterative protocol in which data are collected, a model is trained, and then outputs of that model are used to choose what data to consider next. For example, one data-driven approach…

Machine Learning · Computer Science 2025-04-07 Clara Fannjiang , Stephen Bates , Anastasios N. Angelopoulos , Jennifer Listgarten , Michael I. Jordan

Predicting protein function from sequence is a central challenge in computational biology. While existing methods rely heavily on structured ontologies or similarity-based techniques, they often lack the flexibility to express…

Computational Engineering, Finance, and Science · Computer Science 2025-10-27 Xiao Fei , Michail Chatzianastasis , Sarah Almeida Carneiro , Hadi Abdine , Lawrence P. Petalidis , Michalis Vazirgiannis

Protein design has become a critical method in advancing significant potential for various applications such as drug development and enzyme engineering. However, protein design methods utilizing large language models with solely pretraining…

Artificial Intelligence · Computer Science 2024-12-06 Xiao-Yu Guo , Yi-Fan Li , Yuan Liu , Xiaoyong Pan , Hong-Bin Shen

Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence…

Biomolecules · Quantitative Biology 2021-11-10 Jeanne Trinquier , Guido Uguzzoni , Andrea Pagnani , Francesco Zamponi , Martin Weigt

Recent advances in Protein Language Models (PLMs) have transformed protein engineering, yet unlike their counterparts in Natural Language Processing (NLP), current PLMs exhibit a fundamental limitation: they excel in either Protein Language…

Computational Engineering, Finance, and Science · Computer Science 2025-09-16 Liuzhenghao Lv , Zongying Lin , Hao Li , Yuyang Liu , Jiaxi Cui , Calvin Yu-Chian Chen , Li Yuan , Yonghong Tian

Proteins are fundamental biological entities that play a key role in life activities. The amino acid sequences of proteins can be folded into stable 3D structures in the real physicochemical world, forming a special kind of…

Machine Learning · Computer Science 2023-01-04 Lirong Wu , Yufei Huang , Haitao Lin , Stan Z. Li

Protein language models (pLMs) produce per-residue representations that capture evolutionary and structural information, yet their mean-pooled sequence embeddings are not explicitly trained to reflect functional, evolutionary or structural…

Machine Learning · Computer Science 2026-05-11 Dan Ofer , Oriel Perets , Michal Linial , Nadav Rappoport

Deep learning has deeply influenced protein science, enabling breakthroughs in predicting protein properties, higher-order structures, and molecular interactions. This paper introduces DeepProtein, a comprehensive and user-friendly deep…

Machine Learning · Computer Science 2025-06-17 Jiaqing Xie , Tianfan Fu

Large Language Models (LLMs) have revolutionized the field of natural language processing, but they fall short in comprehending biological sequences such as proteins. To address this challenge, we propose InstructProtein, an innovative LLM…

Biomolecules · Quantitative Biology 2023-10-06 Zeyuan Wang , Qiang Zhang , Keyan Ding , Ming Qin , Xiang Zhuang , Xiaotong Li , Huajun Chen

Statistical analysis of evolutionary-related protein sequences provides insights about their structure, function, and history. We show that Restricted Boltzmann Machines (RBM), designed to learn complex high-dimensional data and their…

Quantitative Methods · Quantitative Biology 2019-02-28 Jérôme Tubiana , Simona Cocco , Rémi Monasson

Accurately modeling the protein fitness landscapes holds great importance for protein engineering. Recently, due to their capacity and representation ability, pre-trained protein language models have achieved state-of-the-art performance in…

Biomolecules · Quantitative Biology 2024-02-06 Ziyi Zhou , Liang Zhang , Yuanxi Yu , Mingchen Li , Liang Hong , Pan Tan

Protein language models are a powerful tool for learning protein representations through pre-training on vast protein sequence datasets. However, traditional protein language models lack explicit structural supervision, despite its…

Biomolecules · Quantitative Biology 2024-02-09 Zuobai Zhang , Jiarui Lu , Vijil Chenthamarakshan , Aurélie Lozano , Payel Das , Jian Tang