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Therapeutic antibodies have been extensively studied in drug discovery and development in the past decades. Antibodies are specialized protective proteins that bind to antigens in a lock-to-key manner. The binding strength/affinity between…

Machine Learning · Computer Science 2024-06-21 Bohao Xu , Yanbo Wang , Wenyu Chen , Shimin Shan

Antibodies are canonically Y-shaped multimeric proteins capable of highly specific molecular recognition. The CDRH3 region located at the tip of variable chains of an antibody dominates antigen-binding specificity. Therefore, it is a…

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…

We report a flexible language-model based deep learning strategy, applied here to solve complex forward and inverse problems in protein modeling, based on an attention neural network that integrates transformer and graph convolutional…

Biomolecules · Quantitative Biology 2023-10-20 Markus J. Buehler

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

We introduce IgDiff, an antibody variable domain diffusion model based on a general protein backbone diffusion framework which was extended to handle multiple chains. Assessing the designability and novelty of the structures generated with…

Biomolecules · Quantitative Biology 2024-05-14 Daniel Cutting , Frédéric A. Dreyer , David Errington , Constantin Schneider , Charlotte M. Deane

The rational design of molecules with desired properties is a long-standing challenge in chemistry. Generative neural networks have emerged as a powerful approach to sample novel molecules from a learned distribution. Here, we propose a…

The SARS-CoV-2 pandemic has created a global race for a cure. One approach focuses on designing a novel variant of the human angiotensin-converting enzyme 2 (ACE2) that binds more tightly to the SARS-CoV-2 spike protein and diverts it from…

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…

The adaptive immune response, largely mediated by B-cell receptors (BCRs), plays a crucial role for effective pathogen neutralization due to its diversity and antigen specificity. Designing BCRs de novo, or from scratch, has been…

Biomolecules · Quantitative Biology 2024-09-11 Desmond Kuan , Amir Barati Farimani

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

Predicting a structure of an antibody from its sequence is important since it allows for a better design process of synthetic antibodies that play a vital role in the health industry. Most of the structure of an antibody is conservative.…

Biomolecules · Quantitative Biology 2021-12-23 Natalia Zenkova , Ekaterina Sedykh , Tatiana Shugaeva , Vladislav Strashko , Timofei Ermak , Aleksei Shpilman

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

With the fast development of COVID-19 into a global pandemic, scientists around the globe are desperately searching for effective antiviral therapeutic agents. Bridging systems biology and drug discovery, we propose a deep learning…

Quantitative Methods · Quantitative Biology 2020-11-24 Jannis Born , Matteo Manica , Joris Cadow , Greta Markert , Nil Adell Mill , Modestas Filipavicius , María Rodríguez Martínez

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

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

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

Computational antibody CDR design methods condition on antigen structure to generate binding loops, yet existing architectures conflate two fundamentally distinct sub-problems: identifying which CDR positions will contact the antigen, and…

Machine Learning · Computer Science 2026-05-22 Mansoor Ahmed , Spencer VonBank , Nadeem Taj , Sujin Lee , Naila Jan , Murray Patterson

The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

We propose generative neural network methods to generate DNA sequences and tune them to have desired properties. We present three approaches: creating synthetic DNA sequences using a generative adversarial network; a DNA-based variant of…

Machine Learning · Computer Science 2017-12-19 Nathan Killoran , Leo J. Lee , Andrew Delong , David Duvenaud , Brendan J. Frey