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Accurate prediction of antibody-antigen (Ab-Ag) binding affinity is essential for therapeutic design and vaccine development, yet the performance of current models is limited by noisy experimental labels, heterogeneous assay conditions, and…

Motivation: The clinical efficacy of antibody therapeutics critically depends on high-affinity target engagement, yet laboratory affinity-maturation campaigns are slow and costly. In computational settings, most protein language models…

Computational Engineering, Finance, and Science · Computer Science 2025-12-22 Xinyan Zhao , Yi-Ching Tang , Rivaaj Monsia , Victor J. Cantu , Ashwin Kumar Ramesh , Xiaozhong Liu , Zhiqiang An , Xiaoqian Jiang , Yejin Kim

Nanobodies -- single-domain antibody fragments derived from camelid heavy-chain-only antibodies -- exhibit unique advantages such as compact size, high stability, and strong binding affinity, making them valuable tools in therapeutics and…

Machine Learning · Computer Science 2025-07-29 Yiming Zhang , Koji Tsuda

Antibody design remains a critical challenge in therapeutic and diagnostic development, particularly for complex antigens with diverse binding interfaces. Current computational methods face two main limitations: (1) capturing geometric…

Machine Learning · Computer Science 2025-06-27 Jiameng Chen , Xiantao Cai , Jia Wu , Wenbin Hu

Accurate prediction of antibody-antigen binding affinity is fundamental to therapeutic design, yet remains constrained by severe label sparsity and the complexity of antigenic variations. In this paper, we propose AbLWR (Antibody-antigen…

Machine Learning · Computer Science 2026-04-14 Fan Xu , Zhi-an Huang , Haohuai He , Yidong Song , Wei Liu , Dongxu Zhang , Yao Hu , Kay Chen Tan

Antigen-antibody binding is a critical process in the immune response. Although recent progress has advanced antibody design, current methods lack a generative framework for end-to-end modeling of full-atom antibody structures and struggle…

Quantitative Methods · Quantitative Biology 2026-02-10 Wenda Wang , Yang Zhang , Zhewei Wei , Wenbing Huang

The computational design of antibodies with high specificity and affinity is a cornerstone of modern therapeutic development. While deep generative models have demonstrated potential, they often struggle to balance high-fidelity geometric…

Quantitative Methods · Quantitative Biology 2026-02-24 Yue Hu , Feng Tao , Junqing Wang , YingChao Liu

Antibody-facilitated immune responses are central to the body's defense against pathogens, viruses, and other foreign invaders. The ability of antibodies to specifically bind and neutralize antigens is vital for maintaining immunity. Over…

Machine Learning · Computer Science 2025-06-12 Delower Hossain , Ehsan Saghapour , Kevin Song , Jake Y. Chen

The design and optimization of antibodies requires an intricate balance across multiple properties. Protein inverse folding models, capable of generating diverse sequences folding into the same structure, are promising tools for maintaining…

In response to pathogens, the adaptive immune system generates specific antibodies that bind and neutralize foreign antigens. Understanding the composition of an individual's immune repertoire can provide insights into this process and…

Biomolecules · Quantitative Biology 2021-12-16 Jeffrey A. Ruffolo , Jeffrey J. Gray , Jeremias Sulam

In recent decades, antibodies have emerged as indispensable therapeutics for combating diseases, particularly viral infections. However, their development has been hindered by limited structural information and labor-intensive engineering…

Biomolecules · Quantitative Biology 2023-09-01 Hongtai Jing , Zhengtao Gao , Sheng Xu , Tao Shen , Zhangzhi Peng , Shwai He , Tao You , Shuang Ye , Wei Lin , Siqi Sun

The development of therapeutic antibodies heavily relies on accurate predictions of how antigens will interact with antibodies. Existing computational methods in antibody design often overlook crucial conformational changes that antigens…

Quantitative Methods · Quantitative Biology 2025-03-05 Cheng Tan , Yijie Zhang , Zhangyang Gao , Yufei Huang , Haitao Lin , Lirong Wu , Fandi Wu , Mathieu Blanchette , Stan. Z. Li

Antibodies are Y-shaped proteins that neutralize pathogens and constitute the core of our adaptive immune system. De novo generation of new antibodies that target specific antigens holds the key to accelerating vaccine discovery. However,…

Machine Learning · Computer Science 2023-06-05 Yogesh Verma , Markus Heinonen , Vikas Garg

The success of therapeutic antibodies relies on their ability to selectively bind antigens. AI-based antibody design protocols have shown promise in generating epitope-specific designs. Many of these protocols use an inverse folding step to…

Quantitative Methods · Quantitative Biology 2023-12-12 Divya Nori , Simon V. Mathis , Amir Shanehsazzadeh

Computational antibody design has seen rapid methodological progress, with dozens of deep generative methods proposed in the past three years, yet the field lacks a standardized benchmark for fair comparison and model development. These…

Machine Learning · Computer Science 2026-04-02 Mansoor Ahmed , Nadeem Taj , Imdad Ullah Khan , Hemanth Venkateswara , Murray Patterson

Affinity maturation produces antibodies that bind antigens with high specificity by accumulating mutations in the antibody sequence. Mapping out the antibody-antigen affinity landscape can give us insight into the accessible paths during…

Populations and Evolution · Quantitative Biology 2019-05-14 Rhys M. Adams , Justin B. Kinney , Aleksandra M. Walczak , Thierry Mora

Protein-ligand binding affinity prediction is essential for drug discovery and toxicity assessment. While machine learning (ML) promises fast and accurate predictions, its progress is constrained by the availability of reliable data. In…

As a research community, we are still lacking a systematic understanding of the progress on adversarial robustness which often makes it hard to identify the most promising ideas in training robust models. A key challenge in benchmarking…

AlphaFold 3 (AF3) is a powerful biomolecular structure-predicting tool based on the latest deep learning algorithms and revolutionized AI model architectures. A few of papers have already investigated its accuracy in predicting different…

Biomolecules · Quantitative Biology 2025-11-19 Yiyang Xu , Ziyou Shen , Yanqing Lv , Shutong Tan , Chun Sun , Juan Zhang

Recent advances in de novo protein binder design have enabled increasing experimental validation, yet reported in silico metrics remain difficult to interpret or compare across studies due to non-standardized evaluation protocols. We…

Quantitative Methods · Quantitative Biology 2026-05-25 Cong Liu , Milong Ren , Jiaqi Guan , Chengyue Gong , Jinyuan Sun , Xinshi Chen , Wenzhi Xiao
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