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We present the MSA-to-protein transformer, a generative model of protein sequences conditioned on protein families represented by multiple sequence alignments (MSAs). Unlike existing approaches to learning generative models of protein…

Biomolecules · Quantitative Biology 2022-04-05 Soumya Ram , Tristan Bepler

Predicting protein-protein interactions from sequences is an important goal of computational biology. Various sources of information can be used to this end. Starting from the sequences of two interacting protein families, one can use…

Biomolecules · Quantitative Biology 2023-04-26 Carlos A. Gandarilla-Perez , Sergio Pinilla , Anne-Florence Bitbol , Martin Weigt

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language…

Biomolecules · Quantitative Biology 2025-06-11 Logan Hallee , Nikolaos Rafailidis , David B. Bichara , Jason P. Gleghorn

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based…

Numerous cellular functions rely on protein$\unicode{x2013}$protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep…

Biomolecules · Quantitative Biology 2023-12-08 Julia R. Rogers , Gergő Nikolényi , Mohammed AlQuraishi

The inapplicability of amino acid covariation methods to small protein families has limited their use for structural annotation of whole genomes. Recently, deep learning has shown promise in allowing accurate residue-residue contact…

Biomolecules · Quantitative Biology 2019-09-10 Joe G Greener , Shaun M Kandathil , David T Jones

Understanding protein-protein interactions is central to our understanding of almost all complex biological processes. Computational tools exploiting rapidly growing genomic databases to characterize protein-protein interactions are…

Quantitative Methods · Quantitative Biology 2016-10-28 Thomas Gueudré , Carlo Baldassi , Marco Zamparo , Martin Weigt , Andrea Pagnani

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein functions. Recent sequence representation learning methods based on Protein Language Models (PLMs) excel in sequence-based…

Quantitative Methods · Quantitative Biology 2023-10-19 Zuobai Zhang , Chuanrui Wang , Minghao Xu , Vijil Chenthamarakshan , Aurélie Lozano , Payel Das , Jian Tang

AI-based protein structure prediction pipelines, such as AlphaFold2, have achieved near-experimental accuracy. These advanced pipelines mainly rely on Multiple Sequence Alignments (MSAs) as inputs to learn the co-evolution information from…

Biomolecules · Quantitative Biology 2023-10-19 Xiaomin Fang , Fan Wang , Lihang Liu , Jingzhou He , Dayong Lin , Yingfei Xiang , Xiaonan Zhang , Hua Wu , Hui Li , Le Song

Protein structures and functions are determined by a contiguous arrangement of amino acid sequences. Designing novel protein sequences and structures with desired geometry and functions is a complex task with large state spaces. Here we…

Chemical Physics · Physics 2022-09-01 Xeerak Agha , Nihang Fu , Jianjun Hu

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Identifying drug-target interactions is essential for developing effective therapeutics. Binding affinity quantifies these interactions, and traditional approaches rely on computationally intensive 3D structural data. In contrast, language…

Quantitative Methods · Quantitative Biology 2024-11-08 Radheesh Sharma Meda , Amir Barati Farimani

The goal of protein representation learning is to extract knowledge from protein databases that can be applied to various protein-related downstream tasks. Although protein sequence, structure, and function are the three key modalities for…

Biomolecules · Quantitative Biology 2024-05-14 Eunji Ko , Seul Lee , Minseon Kim , Dongki Kim

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

Protein inverse folding is a fundamental problem in bioinformatics, aiming to recover the amino acid sequences from a given protein backbone structure. Despite the success of existing methods, they struggle to fully capture the intricate…

Machine Learning · Computer Science 2024-12-13 Chenglin Wang , Yucheng Zhou , Zijie Zhai , Jianbing Shen , Kai Zhang

We explore a framework for protein sequence representation learning that decomposes the task between manifold learning and distributional modelling. Specifically we present a Latent Space Diffusion architecture which combines a protein…

Machine Learning · Computer Science 2025-03-25 Eoin Quinn , Ghassene Jebali , Maxime Seince , Oliver Bent

Deep learning-based prediction of protein-ligand complexes has advanced significantly with the development of architectures such as AlphaFold3, Boltz-1, Chai-1, Protenix, and NeuralPlexer. Multiple sequence alignment (MSA) has been a key…

Biomolecules · Quantitative Biology 2025-06-03 Enming Xing , Junjie Zhang , Shen Wang , Xiaolin Cheng

Accurately measuring protein-RNA binding affinity is crucial in many biological processes and drug design. Previous computational methods for protein-RNA binding affinity prediction rely on either sequence or structure features, unable to…

Biomolecules · Quantitative Biology 2025-01-06 Rong Han , Xiaohong Liu , Tong Pan , Jing Xu , Xiaoyu Wang , Wuyang Lan , Zhenyu Li , Zixuan Wang , Jiangning Song , Guangyu Wang , Ting Chen

Identifying protein-protein interactions is crucial for a systems-level understanding of the cell. Recently, algorithms based on inverse statistical physics, e.g. Direct Coupling Analysis (DCA), have allowed to use evolutionarily related…

Biomolecules · Quantitative Biology 2020-03-25 Carlos A. Gandarilla-Pérez , Pierre Mergny , Martin Weigt , Anne-Florence Bitbol