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Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Ge Wang , Han Zhang , Stan Z. Li

Enzymes are genetically encoded biocatalysts capable of accelerating chemical reactions. How can we automatically design functional enzymes? In this paper, we propose EnzyGen, an approach to learn a unified model to design enzymes across…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Yunlong Zhao , Wenxian Shi , Wengong Jin , Yang Yang , Lei Li

Enzymes are nano-scale machines that have evolved to drive chemical reactions out of equilibrium in the right place at the right time. Given the complexity and specificity of enzymatic function, bottom-up design of enzymes presents a…

Soft Condensed Matter · Physics 2025-05-28 Michalis Chatzittofi , Jaime Agudo-Canalejo , Ramin Golestanian

Enzyme mining is rapidly evolving as a data-driven strategy to identify biocatalysts with tailored functions from the vast landscape of uncharacterized proteins. The integration of machine learning into these workflows enables…

Biomolecules · Quantitative Biology 2025-07-11 Yanzi Zhang , Felix Moorhoff , Sizhe Qiu , Wenjuan Dong , David Medina-Ortiz , Jing Zhao , Mehdi D. Davari

Sparked by innovations in generative artificial intelligence (AI), the field of protein design has undergone a paradigm shift with an explosion of new models for optimizing existing enzymes or creating them from scratch. After more than one…

Biomolecules · Quantitative Biology 2026-02-04 Lasse Middendorf , Noelia Ferruz

The introduction of models like RFDiffusionAA, AlphaFold3, AlphaProteo, and Chai1 has revolutionized protein structure modeling and interaction prediction, primarily from a binding perspective, focusing on creating ideal lock-and-key…

Biomolecules · Quantitative Biology 2024-11-27 Chenqing Hua , Jiarui Lu , Yong Liu , Odin Zhang , Jian Tang , Rex Ying , Wengong Jin , Guy Wolf , Doina Precup , Shuangjia Zheng

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Protein mutations can have profound effects on biological function, making accurate prediction of property changes critical for drug discovery, protein engineering, and precision medicine. Current approaches rely on fine-tuning…

Machine Learning · Computer Science 2025-10-27 Srivathsan Badrinarayanan , Yue Su , Janghoon Ock , Alan Pham , Sanya Ahuja , Amir Barati Farimani

Enzymes, with their specific catalyzed reactions, are necessary for all aspects of life, enabling diverse biological processes and adaptations. Predicting enzyme functions is essential for understanding biological pathways, guiding drug…

Machine Learning · Computer Science 2024-10-02 Chenqing Hua , Bozitao Zhong , Sitao Luan , Liang Hong , Guy Wolf , Doina Precup , Shuangjia Zheng

Designing enzyme backbones with substrate-specific functionality is a critical challenge in computational protein engineering. Current generative models excel in protein design but face limitations in binding data, substrate-specific…

Biomolecules · Quantitative Biology 2025-10-30 Chao Song , Zhiyuan Liu , Han Huang , Liang Wang , Qiong Wang , Jianyu Shi , Hui Yu , Yihang Zhou , Yang Zhang

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Enzyme is the major workhorse to carry out the diverse cellular functions. It catalyzes the biological reactions with a high specificity, with its topology playing a crucial role. For ecologically safe production of numerous bioproducts…

Biomolecules · Quantitative Biology 2021-06-04 Prabha Sankara Narayanan , Ashish Runthala

Genome-scale metabolic models (GEMs) are essential tools for systems biology and rational chassis design, but conventional top-down reconstruction depends heavily on sequence homology and often leaves unknown enzymes and metabolic dark…

Quantitative Methods · Quantitative Biology 2026-05-15 Weiyu Xiao , Jiangbin Zheng , Stan Z. Li

Identifying enzymes that catalyze target biochemical reactions is a key step in computational enzyme discovery and biocatalyst design. Recent representation-learning methods formulate this problem as enzyme--reaction matching, where paired…

Biomolecules · Quantitative Biology 2026-05-26 Gengmo Zhou , Feng Yu , Wenda Wang , Zhifeng Gao , Guolin Ke , Zhewei Wei , Zhen Wang

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

Designing enzymes with substrate-binding pockets is a critical challenge in protein engineering, as catalytic activity depends on the precise interaction between pockets and substrates. Currently, generative models dominate functional…

Biomolecules · Quantitative Biology 2026-01-28 Zefeng Lin , Zhihang Zhang , Weirong Zhu , Tongchang Han , Xianyong Fang , Tianfan Fu , Xiaohua Xu

The enzyme turnover rate is a fundamental parameter in enzyme kinetics, reflecting the catalytic efficiency of enzymes. However, enzyme turnover rates remain scarce across most organisms due to the high cost and complexity of experimental…

Machine Learning · Computer Science 2025-09-16 Bozhen Hu , Cheng Tan , Siyuan Li , Jiangbin Zheng , Sizhe Qiu , Jun Xia , Stan Z. Li

While artificial intelligence has made remarkable strides in revealing the relationship between biological macromolecules' primary sequence and tertiary structure, designing RNA sequences based on specified tertiary structures remains…

Biomolecules · Quantitative Biology 2024-03-08 Cheng Tan , Yijie Zhang , Zhangyang Gao , Bozhen Hu , Siyuan Li , Zicheng Liu , Stan Z. Li

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

Designing RNA molecules has garnered recent interest in medicine, synthetic biology, biotechnology and bioinformatics since many functional RNA molecules were shown to be involved in regulatory processes for transcription, epigenetics and…

Machine Learning · Computer Science 2019-04-15 Frederic Runge , Danny Stoll , Stefan Falkner , Frank Hutter
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