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The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Flavio Seno , Jayanth Banavar , Amos Maritan

Unlocking the next generation of biotechnology and therapeutic innovation demands overcoming the inherent complexity and resource-intensity of conventional protein engineering methods. Recent GenAI-powered computational techniques often…

Protein language models (PLMs) have shown promise in improving the understanding of protein sequences, contributing to advances in areas such as function prediction and protein engineering. However, training these models from scratch…

Machine Learning · Computer Science 2024-12-19 Shivasankaran Vanaja Pandi , Bharath Ramsundar

Predicting protein-protein interactions (PPIs) by learning informative representations from amino acid sequences is a challenging yet important problem in biology. Although various deep learning models in Siamese architecture have been…

Machine Learning · Computer Science 2020-10-19 Kishan KC , Feng Cui , Anne Haake , Rui Li

Accurately predicting protein melting temperature changes (Delta Tm) is fundamental for assessing protein stability and guiding protein engineering. Leveraging multi-modal protein representations has shown great promise in capturing the…

Machine Learning · Computer Science 2025-03-25 Daiheng Zhang , Yan Zeng , Xinyu Hong , Jinbo Xu

Recent advancements in unsupervised protein language models (ProteinLMs), like ESM-1b and ESM-2, have shown promise in different protein prediction tasks. However, these models face challenges due to their high computational demands,…

Machine Learning · Computer Science 2023-10-31 Shuang Peng , Fei Yang , Ning Sun , Sheng Chen , Yanfeng Jiang , Aimin Pan

Deciphering the function of unseen protein sequences is a fundamental challenge with broad scientific impact, yet most existing methods depend on task-specific adapters or large-scale supervised fine-tuning. We introduce the…

Machine Learning · Computer Science 2025-10-14 Xinhui Chen , Zuchao Li , Mengqi Gao , Yufeng Zhang , Chak Tou Leong , Haoyang Li , Jiaqi Chen

Various approaches utilizing Transformer architectures have achieved state-of-the-art results in Natural Language Processing (NLP). Based on this success, numerous architectures have been proposed for other types of data, such as in…

Machine Learning · Computer Science 2025-01-15 Gabriel Bianchin de Oliveira , Helio Pedrini , Zanoni Dias

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due…

Computation and Language · Computer Science 2021-11-01 Liang He , Shizhuo Zhang , Lijun Wu , Huanhuan Xia , Fusong Ju , He Zhang , Siyuan Liu , Yingce Xia , Jianwei Zhu , Pan Deng , Bin Shao , Tao Qin , Tie-Yan Liu

Accurate identification of interactions between protein residues and ligand functional groups is essential to understand molecular recognition and guide rational drug design. Existing deep learning approaches for protein-ligand…

Machine Learning · Computer Science 2025-09-04 Phuc Pham , Viet Thanh Duy Nguyen , Truong-Son Hy

Protein language models have revolutionized structure prediction, but their nonlinear nature obscures how sequence representations inform structure prediction. While sparse autoencoders (SAEs) offer a path to interpretability here by…

Biomolecules · Quantitative Biology 2025-03-13 Nithin Parsan , David J. Yang , John J. Yang

Protein interactions are important in a broad range of biological processes. Traditionally, computational methods have been developed to automatically predict protein interface from hand-crafted features. Recent approaches employ deep…

Machine Learning · Computer Science 2020-07-21 Yi Liu , Hao Yuan , Lei Cai , Shuiwang Ji

Protein language models have excelled in a variety of tasks, ranging from structure prediction to protein engineering. However, proteins are highly diverse in functions and structures, and current state-of-the-art models including the…

Biomolecules · Quantitative Biology 2023-02-27 Chang Ma , Haiteng Zhao , Lin Zheng , Jiayi Xin , Qintong Li , Lijun Wu , Zhihong Deng , Yang Lu , Qi Liu , Lingpeng Kong

Computational biology and bioinformatics provide vast data gold-mines from protein sequences, ideal for Language Models taken from NLP. These LMs reach for new prediction frontiers at low inference costs. Here, we trained two…

While protein language models (PLMs) are one of the most promising avenues of research for future de novo protein design, the way in which they transform sequences to hidden representations, as well as the information encoded in such…

Machine Learning · Computer Science 2026-05-29 Kosio Beshkov , Anders Malthe-Sørenssen

The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…

Populations and Evolution · Quantitative Biology 2015-06-22 Mathieu Hemery , Olivier Rivoire

Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

Protein-protein interactions (PPIs) are associated with various diseases, including cancer, infections, and neurodegenerative disorders. Obtaining three-dimensional structural information on these PPIs serves as a foundation to interfere…

Biomolecules · Quantitative Biology 2024-07-24 Xiaotong Xu , Alexandre M. J. J. Bonvin

Specific protein-protein interactions are crucial in the cell, both to ensure the formation and stability of multi-protein complexes, and to enable signal transduction in various pathways. Functional interactions between proteins result in…

Biological Physics · Physics 2016-11-21 Anne-Florence Bitbol , Robert S. Dwyer , Lucy J. Colwell , Ned S. Wingreen

Protein-Protein Interactions (PPIs) are fundamental in various biological processes and play a key role in life activities. The growing demand and cost of experimental PPI assays require computational methods for efficient PPI prediction.…

Machine Learning · Computer Science 2024-02-23 Lirong Wu , Yijun Tian , Yufei Huang , Siyuan Li , Haitao Lin , Nitesh V Chawla , Stan Z. Li