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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

Computational protein design, i.e. inferring novel and diverse protein sequences consistent with a given structure, remains a major unsolved challenge. Recently, deep generative models that learn from sequences alone or from sequences and…

Biomolecules · Quantitative Biology 2021-11-15 Igor Melnyk , Payel Das , Vijil Chenthamarakshan , Aurelie Lozano

Antibodies are versatile proteins that bind to pathogens like viruses and stimulate the adaptive immune system. The specificity of antibody binding is determined by complementarity-determining regions (CDRs) at the tips of these Y-shaped…

Biomolecules · Quantitative Biology 2022-01-31 Wengong Jin , Jeremy Wohlwend , Regina Barzilay , Tommi Jaakkola

Therapeutic antibodies require not only high-affinity target engagement, but also favorable manufacturability, stability, and safety profiles for clinical effectiveness. These properties are collectively called `developability'. To enable a…

Machine Learning · Computer Science 2025-07-04 Siqi Zhao , Joshua Moller , Porfi Quintero-Cadena , Lood van Niekerk

Antibodies are versatile proteins that can bind to pathogens and provide effective protection for human body. Recently, deep learning-based computational antibody design has attracted popular attention since it automatically mines the…

Biomolecules · Quantitative Biology 2022-11-18 Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Tianbo Peng , Yingce Xia , Liang He , Shufang Xie , Tao Qin , Haiguang Liu , Kun He , Tie-Yan Liu

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

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

In arbitrary-order language models, it is an open question how to sample tokens in parallel from the correct joint distribution. With discrete diffusion models, the more tokens they generate in parallel, the less their predicted…

Machine Learning · Computer Science 2025-04-30 Gabe Guo , Stefano Ermon

We consider the problem of antibody sequence design given 3D structural information. Building on previous work, we propose a fine-tuned inverse folding model that is specifically optimised for antibody structures and outperforms generic…

Biomolecules · Quantitative Biology 2023-10-31 Frédéric A. Dreyer , Daniel Cutting , Constantin Schneider , Henry Kenlay , Charlotte M. Deane

Multispecific antibodies offer transformative therapeutic potential by engaging multiple epitopes simultaneously, yet their efficacy is an emergent property governed by complex molecular architectures. Rational design is often bottlenecked…

We introduce AbDiffuser, an equivariant and physics-informed diffusion model for the joint generation of antibody 3D structures and sequences. AbDiffuser is built on top of a new representation of protein structure, relies on a novel…

Structure-Based Drug Design (SBDD) has revolutionized drug discovery by enabling the rational design of molecules for specific protein targets. Despite significant advancements in improving docking scores, advanced 3D-SBDD generative models…

Biomolecules · Quantitative Biology 2025-03-04 Bowen Gao , Yanwen Huang , Yiqiao Liu , Wenxuan Xie , Wei-Ying Ma , Ya-Qin Zhang , Yanyan Lan

Antibodies are essential proteins responsible for immune responses in organisms, capable of specifically recognizing antigen molecules of pathogens. Recent advances in generative models have significantly enhanced rational antibody design.…

Artificial Intelligence · Computer Science 2025-11-10 Zichen Wang , Yaokun Ji , Jianing Tian , Shuangjia Zheng

Advancements in deep generative models have enabled the joint modeling of antibody sequence and structure, given the antigen-antibody complex as context. However, existing approaches for optimizing complementarity-determining regions (CDRs)…

Machine Learning · Computer Science 2025-08-18 Yinghua Yao , Yuangang Pan , Xixian Chen

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Therapeutic antibody development has become an increasingly popular approach for drug development. To date, antibody therapeutics are largely developed using large scale experimental screens of antibody libraries containing hundreds of…

Quantitative Methods · Quantitative Biology 2022-10-07 Lin Li , Esther Gupta , John Spaeth , Leslie Shing , Tristan Bepler , Rajmonda Sulo Caceres

Structure-based drug design (SBDD), which aims to generate 3D ligand molecules binding to target proteins, is a fundamental task in drug discovery. Existing SBDD methods typically treat protein as rigid and neglect protein structural change…

Biomolecules · Quantitative Biology 2024-10-01 Zaixi Zhang , Mengdi Wang , Qi Liu

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

Generative models of macromolecules carry abundant and impactful implications for industrial and biomedical efforts in protein engineering. However, existing methods are currently limited to modeling protein structures or sequences,…

Biomolecules · Quantitative Biology 2024-01-15 Alex Morehead , Jeffrey Ruffolo , Aadyot Bhatnagar , Ali Madani

The increasing scale and complexity of large language models (LLMs) pose significant inference latency challenges, primarily due to their autoregressive decoding paradigm characterized by the sequential nature of next-token prediction. By…

Computation and Language · Computer Science 2025-08-15 Keyu Chen , Zhifeng Shen , Daohai Yu , Haoqian Wu , Wei Wen , Jianfeng He , Ruizhi Qiao , Xing Sun
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