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Current Large Language Models (LLMs) for understanding proteins primarily treats amino acid sequences as a text modality. Meanwhile, Protein Language Models (PLMs), such as ESM-2, have learned massive sequential evolutionary knowledge from…

Machine Learning · Computer Science 2024-12-17 Nuowei Liu , Changzhi Sun , Tao Ji , Junfeng Tian , Jianxin Tang , Yuanbin Wu , Man Lan

Protein language models (PLMs) have advanced computational protein science through large-scale pretraining and scalable architectures. In parallel, reinforcement learning (RL) has broadened exploration and enabled precise multi-objective…

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in…

Quantitative Methods · Quantitative Biology 2024-07-09 Yiqing Shen , Zan Chen , Michail Mamalakis , Luhan He , Haiyang Xia , Tianbin Li , Yanzhou Su , Junjun He , Yu Guang Wang

This paper provides a comprehensive survey of the latest research on multilingual large language models (MLLMs). MLLMs not only are able to understand and generate language across linguistic boundaries, but also represent an important…

Computation and Language · Computer Science 2024-11-20 Shaolin Zhu , Supryadi , Shaoyang Xu , Haoran Sun , Leiyu Pan , Menglong Cui , Jiangcun Du , Renren Jin , António Branco , Deyi Xiong

With the exponential increase of the protein sequence databases over time, multiple-sequence alignment (MSA) methods, like PSI-BLAST, perform exhaustive and time-consuming database search to retrieve evolutionary information. The resulting…

Quantitative Methods · Quantitative Biology 2023-08-21 Issar Arab

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Large language models (LLMs) are a class of artificial intelligence models based on deep learning, which have great performance in various tasks, especially in natural language processing (NLP). Large language models typically consist of…

Quantitative Methods · Quantitative Biology 2025-02-04 Jiajia Liu , Mengyuan Yang , Yankai Yu , Haixia Xu , Tiangang Wang , Kang Li , Xiaobo Zhou

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language…

Biomolecules · Quantitative Biology 2025-06-11 Logan Hallee , Nikolaos Rafailidis , David B. Bichara , Jason P. Gleghorn

Recently, Large Language Models (LLMs) have showcased remarkable capabilities in natural language understanding. While demonstrating proficiency in everyday conversations and question-answering situations, these models frequently struggle…

Computation and Language · Computer Science 2023-08-28 Chaoyi Wu , Weixiong Lin , Xiaoman Zhang , Ya Zhang , Yanfeng Wang , Weidi Xie

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

The 21st century is presenting humankind with unprecedented environmental and medical challenges. The ability to design novel proteins tailored for specific purposes could transform our ability to respond timely to these issues. Recent…

Biomolecules · Quantitative Biology 2022-08-24 Noelia Ferruz , Birte Höcker

Language modeling studies the probability distributions over strings of texts. It is one of the most fundamental tasks in natural language processing (NLP). It has been widely used in text generation, speech recognition, machine…

Computation and Language · Computer Science 2024-07-18 Chengwei Wei , Yun-Cheng Wang , Bin Wang , C. -C. Jay Kuo

Proteins are the essential drivers of biological processes. At the molecular level, they are chains of amino acids that can be viewed through a linguistic lens where the twenty standard residues serve as an alphabet combining to form a…

Computation and Language · Computer Science 2025-12-15 Burak Suyunu , Özdeniz Dolu , Ibukunoluwa Abigail Olaosebikan , Hacer Karatas Bristow , Arzucan Özgür

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due…

Computation and Language · Computer Science 2021-11-01 Liang He , Shizhuo Zhang , Lijun Wu , Huanhuan Xia , Fusong Ju , He Zhang , Siyuan Liu , Yingce Xia , Jianwei Zhu , Pan Deng , Bin Shao , Tao Qin , Tie-Yan Liu

Protein language models (pLMs) excel in a variety of tasks that range from structure prediction to the design of functional enzymes. However, these models operate as black boxes, and their underlying working principles remain unclear. Here,…

Biomolecules · Quantitative Biology 2025-12-08 Andrea Hunklinger , Noelia Ferruz

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…

Biomolecules · Quantitative Biology 2025-03-14 Zicheng Ma , Chuanliu Fan , Zhicong Wang , Zhenyu Chen , Xiaohan Lin , Yanheng Li , Shihao Feng , Jun Zhang , Ziqiang Cao , Yi Qin Gao

Motivation: Proteins are of great significance in living organisms. However, understanding their functions encounters numerous challenges, such as insufficient integration of multimodal information, a large number of training parameters,…

Machine Learning · Computer Science 2025-05-23 Zhicong Wang , Zicheng Ma , Ziqiang Cao , Changlong Zhou , Jun Zhang , Yiqin Gao

Understanding protein solubility is essential for their functional applications. Computational methods for predicting protein solubility are crucial for reducing experimental costs and enhancing the efficiency and success rates of protein…

Quantitative Methods · Quantitative Biology 2024-07-01 Yang Tan , Jia Zheng , Liang Hong , Bingxin Zhou

Pre-trained large language models(LLMs) have attracted increasing attention in biomedical domains due to their success in natural language processing. However, the complex traits and heterogeneity of multi-sources genomics data pose…

Computation and Language · Computer Science 2025-11-25 Yanjun Lyu , Zihao Wu , Lu Zhang , Jing Zhang , Yiwei Li , Wei Ruan , Zhengliang Liu , Zeyu Zhang , Xiang Li , Rongjie Liu , Chao Huang , Wentao Li , Tianming Liu , Dajiang Zhu

Protein language models (PLMs) have enabled advances in structure prediction and de novo protein design, yet they frequently collapse into pathological repetition during generation. Unlike in text, where repetition merely reduces…

Biomolecules · Quantitative Biology 2026-02-03 Jiahao Zhang , Zeqing Zhang , Di Wang , Lijie Hu