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Predicting the binding affinity between antigens and antibodies is fundamental to drug discovery and vaccine development. Traditional computational approaches often rely on experimentally determined 3D structures, which are scarce and…

Machine Learning · Computer Science 2025-12-29 Aicha Boutorh , Soumia Bouyahiaoui , Sara Belhadj , Nour El Yakine Guendouz , Manel Kara Laouar

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Investigating conformational landscapes of proteins is a crucial way to understand their biological functions and properties. AlphaFlow stands out as a sequence-conditioned generative model that introduces flexibility into structure…

Machine Learning · Computer Science 2024-07-18 Shaoning Li , Mingyu Li , Yusong Wang , Xinheng He , Nanning Zheng , Jian Zhang , Pheng-Ann Heng

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 primary objective of most lead optimization campaigns is to enhance the binding affinity of ligands. For large molecules such as antibodies, identifying mutations that enhance antibody affinity is particularly challenging due to the…

Machine Learning · Computer Science 2024-06-12 Alexandra Gessner , Sebastian W. Ober , Owen Vickery , Dino Oglić , Talip Uçar

Antibody therapeutics has been extensively studied in drug discovery and development within the past decades. One increasingly popular focus in the antibody discovery pipeline is the optimization step for therapeutic leads. Both traditional…

Biomolecules · Quantitative Biology 2022-08-16 Yue Kang , Dawei Leng , Jinjiang Guo , Lurong Pan

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…

Antibodies are proteins produced by the immune system that recognize and bind to specific antigens, and their 3D structures are crucial for understanding their binding mechanism and designing therapeutic interventions. The specificity of…

Machine Learning · Computer Science 2024-10-23 Jiying Zhang , Zijing Liu , Shengyuan Bai , He Cao , Yu Li , Lei Zhang

Predicting the binding affinity of protein protein complexes directly from sequence remains a challenging problem, particularly in the absence of reliable structural information. Here I present ProtT Affinity, a sequence only model that…

Quantitative Methods · Quantitative Biology 2025-11-21 Hongfu Lou

A pivotal area of research in antibody engineering is to find effective modifications that enhance antibody-antigen binding affinity. Traditional wet-lab experiments assess mutants in a costly and time-consuming manner. Emerging deep…

Quantitative Methods · Quantitative Biology 2025-05-28 Chen Liu , Mingchen Li , Yang Tan , Wenrui Gou , Guisheng Fan , Bingxin Zhou

Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

Therapeutic antibody candidates often require extensive engineering to improve key functional and developability properties before clinical development. This can be achieved through iterative design, where starting molecules are optimized…

Machine Learning · Computer Science 2025-09-23 Aniruddh Raghu , Sebastian Ober , Maxwell Kazman , Hunter Elliott

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

The growing significance of RNA engineering in diverse biological applications has spurred interest in developing AI methods for structure-based RNA design. While diffusion models have excelled in protein design, adapting them for RNA…

Biomolecules · Quantitative Biology 2024-06-11 Divya Nori , Wengong Jin

Antibodies offer great potential for the treatment of various diseases. However, the discovery of therapeutic antibodies through traditional wet lab methods is expensive and time-consuming. The use of generative models in designing…

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

B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e. in the same "clonal family")…

Biomolecules · Quantitative Biology 2018-11-21 Amrit Dhar , Kristian Davidsen , Frederick A. Matsen , Vladimir N. Minin

We analyze the interactions between division, mutation and selection in a simplified evolutionary model, assuming that the population observed can be classified into fitness levels. The construction of our mathematical framework is…

Probability · Mathematics 2018-01-04 Irene Balelli , Vuk Milišić , Gilles Wainrib

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

Flow-matching models deliver state-of-the-art fidelity in image and video generation, but the inherent sequential denoising process renders them slower. Existing acceleration methods like distillation, trajectory truncation, and consistency…

Computer Vision and Pattern Recognition · Computer Science 2026-02-12 Divya Jyoti Bajpai , Dhruv Bhardwaj , Soumya Roy , Tejas Duseja , Harsh Agarwal , Aashay Sandansing , Manjesh Kumar Hanawal
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