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Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated…

Antibodies play a central role in the immune response by specifically recognizing and neutralizing antigens, and therapeutic antibodies have become major drugs for cancer and autoimmune diseases. However, their discovery still relies on…

Quantitative Methods · Quantitative Biology 2026-05-29 Xiao Luo

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

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4…

Biomolecules · Quantitative Biology 2023-05-04 Sergio Romero-Romero , Sebastian Lindner , Noelia Ferruz

Equivariant graph neural network (GNN) methods for antibody complementarity-determining region (CDR) design achieve the highest sequence recovery but suffer from severe vocabulary collapse. The current best GNN methods over-predict very few…

Machine Learning · Computer Science 2026-05-21 Mansoor Ahmed , Sujin Lee , Umar Khayaz , Murray Patterson

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

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Protein language models often take into consideration the alignment between a protein sequence and its textual description. However, they do not take structural information into consideration. Traditional methods treat sequence and…

Machine Learning · Computer Science 2026-03-10 Aditya Ranganath , Hasin Us Sami , Kowshik Thopalli , Bhavya Kailkhura , Wesam Sakla

Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

Representation learning and \emph{de novo} generation of proteins are pivotal computational biology tasks. Whilst natural language processing (NLP) techniques have proven highly effective for protein sequence modelling, structure modelling…

Quantitative Methods · Quantitative Biology 2025-01-08 Benoit Gaujac , Jérémie Donà , Liviu Copoiu , Timothy Atkinson , Thomas Pierrot , Thomas D. Barrett

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…

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as…

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

Designing proteins de novo with tailored structural, physicochemical, and functional properties remains a grand challenge in biotechnology, medicine, and materials science, due to the vastness of sequence space and the complex coupling…

Artificial Intelligence · Computer Science 2025-12-01 Fiona Y. Wang , Di Sheng Lee , David L. Kaplan , Markus J. Buehler

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential…

Machine Learning · Computer Science 2023-02-10 Zaixiang Zheng , Yifan Deng , Dongyu Xue , Yi Zhou , Fei YE , Quanquan Gu

The 21st century is presenting humankind with unprecedented environmental and medical challenges. The ability to design novel proteins tailored for specific purposes could transform our ability to respond timely to these issues. Recent…

Biomolecules · Quantitative Biology 2022-08-24 Noelia Ferruz , Birte Höcker

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

Large Language Models have demonstrated remarkable capabilities in generating contextually relevant and grammatically correct text. However, they fundamentally lack the ability to process and respond to emotional context in a manner…

Neural and Evolutionary Computing · Computer Science 2026-05-15 Eslam Reda , Sara El-Metwally

Current antibody language models are limited by their use of unpaired antibody sequence data and the biases in publicly available antibody sequence datasets, which are skewed toward antibodies against a relatively small number of pathogens.…

Biomolecules · Quantitative Biology 2023-11-08 Sarah M. Burbach , Bryan Briney