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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

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 determination is essential to a mechanistic understanding of diseases and the development of novel therapeutics. Machine-learning-based structure prediction methods have made significant advancements by computationally predicting…

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

To build effective therapeutics, biologists iteratively mutate antibody sequences to improve binding and stability. Proposed mutations can be informed by previous measurements or by learning from large antibody databases to predict only…

Antibody-based therapeutics-including antibody-drug conjugates (ADCs), bispecific antibodies, and novel formats-are reshaping oncology, yet key determinants of efficacy, safety, and manufacturability frequently emerge after conjugation and…

Soft Condensed Matter · Physics 2026-05-18 Alberto Ocana , Jorge R. Espinosa

Fast and accurate generation of molecular conformers is desired for downstream computational chemistry and drug discovery tasks. Currently, training and sampling state-of-the-art diffusion or flow-based models for conformer generation…

In the recent years, therapeutic use of antibodies has seen a huge growth, due to their inherent proprieties and technological advances in the methods used to study and characterize them. Effective design and engineering of antibodies for…

Biomolecules · Quantitative Biology 2020-05-08 Francesco Ambrosetti , Zuzana Jandova , Alexandre M. J. J. Bonvin

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

Accurate prediction of antibody-binding sites (epitopes) on antigens is crucial for vaccine design, immunodiagnostics, therapeutic antibody development, antibody engineering, research into autoimmune and allergic diseases, and advancing our…

Biomolecules · Quantitative Biology 2025-12-24 Zhangyu You , Jiahao Ma , Hongzong Li , Ye-Fan Hu , Jian-Dong Huang

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

Understanding the intertwined contributions of amino acid sequence and spatial structure is essential to explain protein behaviour. Here, we introduce INFUSSE (Integrated Network Framework Unifying Structure and Sequence Embeddings), a deep…

Quantitative Methods · Quantitative Biology 2025-11-07 Kevin Michalewicz , Mauricio Barahona , Barbara Bravi

Sampling useful three-dimensional molecular structures along with their most favorable conformations is a key challenge in drug discovery. Current state-of-the-art 3D de-novo design flow matching or diffusion-based models are limited to…

Machine Learning · Computer Science 2025-11-24 Riccardo Tedoldi , Ola Engkvist , Patrick Bryant , Hossein Azizpour , Jon Paul Janet , Alessandro Tibo

Antibody design is an essential yet challenging task in various domains like therapeutics and biology. There are two major defects in current learning-based methods: 1) tackling only a certain subtask of the whole antibody design pipeline,…

Biomolecules · Quantitative Biology 2023-05-31 Xiangzhe Kong , Wenbing Huang , Yang Liu

Modern therapeutic antibody design often involves composing multi-part assemblages of individual functional domains, each of which may be derived from a different source or engineered independently. While these complex formats can expand…

Machine Learning · Computer Science 2025-09-25 Jiayi Xin , Aniruddh Raghu , Nick Bhattacharya , Adam Carr , Melanie Montgomery , Hunter Elliott

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

Computational antibody design holds immense promise for therapeutic discovery, yet existing generative models are fundamentally limited by two core challenges: (i) a lack of dynamical consistency, which yields physically implausible…

Machine Learning · Computer Science 2025-11-06 Jiameng Chen , Yida Xiong , Kun Li , Hongzhi Zhang , Xiantao Cai , Wenbin Hu , Jia Wu

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 3D conformation of small molecules within protein binding sites is a key challenge in drug design. When a crystallized reference ligand (template) is available, it provides geometric priors that can guide 3D pose prediction.…

Biomolecules · Quantitative Biology 2025-10-03 Noémie Bergues , Arthur Carré , Paul Join-Lambert , Brice Hoffmann , Arnaud Blondel , Hamza Tajmouati

This chapter describes the application of constrained geometric simulations for prediction of antibody structural dynamics. We utilize constrained geometric simulations method FRODAN, which is a low computational complexity alternative to…

Biomolecules · Quantitative Biology 2021-10-01 Andrejs Tucs , Koji Tsuda , Adnan Sljoka