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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

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

Generative models in molecular design tend to be richly parameterized, data-hungry neural models, as they must create complex structured objects as outputs. Estimating such models from data may be challenging due to the lack of sufficient…

Machine Learning · Computer Science 2021-08-17 Kevin Yang , Wengong Jin , Kyle Swanson , 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

Recently, deep learning has made rapid progress in antibody design, which plays a key role in the advancement of therapeutics. A dominant paradigm is to train a model to jointly generate the antibody sequence and the structure as a…

Quantitative Methods · Quantitative Biology 2025-01-20 Nayoung Kim , Minsu Kim , Sungsoo Ahn , Jinkyoo Park

Antibody therapeutics are among the most successful modern medicines, yet computationally designing antibodies with desirable binding and developability properties remains challenging. While protein language models (pLMs) have emerged as…

Machine Learning · Computer Science 2026-05-11 Justin Sanders , Luca Giancardo , Lan Guo , Yue Zhao , Kemal Sonmez , Nina Cheng , Melih Yilmaz

Antibody design, a crucial task with significant implications across various disciplines such as therapeutics and biology, presents considerable challenges due to its intricate nature. In this paper, we tackle antigen-specific antibody…

Biomolecules · Quantitative Biology 2024-10-29 Xiangxin Zhou , Dongyu Xue , Ruizhe Chen , Zaixiang Zheng , Liang Wang , Quanquan Gu

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

The recognition of the importance of drug-like properties beyond potency to reduce clinical attrition of biologics has driven significant progress in the development of in vitro and in silico tools for developability assessment of antibody…

Biomolecules · Quantitative Biology 2023-05-15 Andreas Evers , Shipra Malhotra , Vanita D. Sood

The idea of using deep-learning-based molecular generation to accelerate discovery of drug candidates has attracted extraordinary attention, and many deep generative models have been developed for automated drug design, termed molecular…

Biomolecules · Quantitative Biology 2024-05-01 Odin Zhang , Haitao Lin , Hui Zhang , Huifeng Zhao , Yufei Huang , Yuansheng Huang , Dejun Jiang , Chang-yu Hsieh , Peichen Pan , Tingjun Hou

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

Bayesian optimization is a natural candidate for the engineering of antibody therapeutic properties, which is often iterative and expensive. However, finding the optimal choice of surrogate model for optimization over the highly structured…

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…

Recent advances in diffusion models have shown remarkable potential for antibody design, yet existing approaches apply uniform generation strategies that cannot adapt to each antigen's unique requirements. Inspired by B cell affinity…

Machine Learning · Computer Science 2025-08-19 Hanqi Feng , Peng Qiu , Mengchun Zhang , Yiran Tao , You Fan , Jingtao Xu , Barnabas Poczos

Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…

Biomolecules · Quantitative Biology 2026-02-27 Filippo Stocco , Michele Garibbo , Noelia Ferruz

Antibody therapies have been employed to address some of today's most challenging diseases, but must meet many criteria during drug development before reaching a patient. Humanization is a sequence optimization strategy that addresses one…

Machine Learning · Computer Science 2024-12-10 Cade Gordon , Aniruddh Raghu , Peyton Greenside , Hunter Elliott

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

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

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

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
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