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Proteins are macromolecules responsible for essential functions in almost all living organisms. Designing reasonable proteins with desired functions is crucial. A protein's sequence and structure are strongly correlated and they together…

Machine Learning · Computer Science 2024-01-10 Zhenqiao Song , Yunlong Zhao , Wenxian Shi , Yang Yang , Lei Li

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential…

Machine Learning · Computer Science 2023-02-10 Zaixiang Zheng , Yifan Deng , Dongyu Xue , Yi Zhou , Fei YE , Quanquan Gu

Learning meaningful protein representation is important for a variety of biological downstream tasks such as structure-based drug design. Having witnessed the success of protein sequence pretraining, pretraining for structural data which is…

Machine Learning · Computer Science 2023-02-23 Yufei Huang , Lirong Wu , Haitao Lin , Jiangbin Zheng , Ge Wang , Stan Z. Li

Structural biology has long been dominated by the one sequence, one structure, one function paradigm, yet many critical biological processes - from enzyme catalysis to membrane transport - depend on proteins that adopt multiple…

Proteins perform their biological functions through three-dimensional structures encoded by amino acid sequences, and ligand-binding protein co-design requires models that generate sequence-structure compatible proteins under explicit…

Biomolecules · Quantitative Biology 2026-05-28 Chen Wei , Fanding Xu , Minghao Sun , Zhiyuan Liu , Lin Wang , Tianrui Jia , Yihang Zhou , Yang Zhang

Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or…

Protein language models often take into consideration the alignment between a protein sequence and its textual description. However, they do not take structural information into consideration. Traditional methods treat sequence and…

Machine Learning · Computer Science 2026-03-10 Aditya Ranganath , Hasin Us Sami , Kowshik Thopalli , Bhavya Kailkhura , Wesam Sakla

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological…

Biomolecules · Quantitative Biology 2025-04-24 Yujie Qin , Ming He , Changyong Yu , Ming Ni , Xian Liu , Xiaochen Bo

We theorize that phylogenetic profiles provide a quantitative method that can relate the structural and functional properties of proteins, as well as their evolutionary relationships. A key feature of phylogenetic profiles is the…

Quantitative Methods · Quantitative Biology 2009-11-04 Yoojin Hong , Jaewoo Kang , Dongwon Lee , Randen L. Patterson , Damian B. van Rossum

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design…

Machine Learning · Computer Science 2026-03-03 Ziwen Wang , Jiajun Fan , Ruihan Guo , Thao Nguyen , Heng Ji , Ge Liu

Despite significant progress in static protein structure collection and prediction, the dynamic behavior of proteins, one of their most vital characteristics, has been largely overlooked in prior research. This oversight can be attributed…

Biomolecules · Quantitative Biology 2024-09-19 Ce Liu , Jun Wang , Zhiqiang Cai , Yingxu Wang , Huizhen Kuang , Kaihui Cheng , Liwei Zhang , Qingkun Su , Yining Tang , Fenglei Cao , Limei Han , Siyu Zhu , Yuan Qi

Understanding the relationships between protein sequence, structure and function is a long-standing biological challenge with manifold implications from drug design to our understanding of evolution. Recently, protein language models have…

Quantitative Methods · Quantitative Biology 2024-01-29 Dexiong Chen , Philip Hartout , Paolo Pellizzoni , Carlos Oliver , Karsten Borgwardt

Proteins inherently possess a consistent sequence-structure duality. The abundance of protein sequence data, which can be readily represented as discrete tokens, has driven fruitful developments in protein language models (pLMs). A key…

Computational Engineering, Finance, and Science · Computer Science 2026-05-29 Yi Zhou , Haohao Qu , Yunqing Liu , Shanru Lin , Le Song , Wenqi Fan

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

Recent advancements in machine learning techniques for protein folding motivate better results in its inverse problem -- protein design. In this work we introduce a new graph mimetic neural network, MimNet, and show that it is possible to…

Biomolecules · Quantitative Biology 2021-02-09 Moshe Eliasof , Tue Boesen , Eldad Haber , Chen Keasar , Eran Treister

Protein representation learning methods have shown great potential to yield useful representation for many downstream tasks, especially on protein classification. Moreover, a few recent studies have shown great promise in addressing…

Machine Learning · Computer Science 2023-04-11 Can Chen , Jingbo Zhou , Fan Wang , Xue Liu , Dejing Dou

The idea of this project is to study the protein structure and sequence relationship using the hidden markov model and artificial neural network. In this context we have assumed two hidden markov models. In first model we have taken protein…

Machine Learning · Computer Science 2012-06-18 Saurabh Sarkar , Prateek Malhotra , Virender Guman

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray