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Retrieving homologous protein sequences is essential for a broad range of protein modeling tasks such as fitness prediction, protein design, structure modeling, and protein-protein interactions. Traditional workflows have relied on a…

Quantitative Methods · Quantitative Biology 2025-06-11 Ruben Weitzman , Peter Mørch Groth , Lood Van Niekerk , Aoi Otani , Yarin Gal , Debora Marks , Pascal Notin

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

Sequence generative models are transforming protein engineering. However, no principled framework exists for conditioning these models on auxiliary information, such as experimental data, without additional training of a generative model.…

Machine Learning · Computer Science 2026-01-19 Junhao Xiong , Ishan Gaur , Maria Lukarska , Hunter Nisonoff , Luke M. Oltrogge , David F. Savage , Jennifer Listgarten

A large number of protein sequences are becoming available through the application of novel high-throughput sequencing technologies. Experimental functional characterization of these proteins is time-consuming and expensive, and is often…

Genomics · Quantitative Biology 2017-09-28 Maxat Kulmanov , Mohammed Asif Khan , Robert Hoehndorf

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled…

Diffusion and flow-matching models achieve remarkable generative performance but at the cost of many sampling steps, this slows inference and limits applicability to time-critical tasks. The ReFlow procedure can accelerate sampling by…

Machine Learning · Computer Science 2024-10-11 Beomsu Kim , Yu-Guan Hsieh , Michal Klein , Marco Cuturi , Jong Chul Ye , Bahjat Kawar , James Thornton

Flow matching models have emerged as a powerful method for generative modeling on domains like images or videos, and even on irregular or unstructured data like 3D point clouds or even protein structures. These models are commonly trained…

Machine Learning · Computer Science 2025-05-30 Yuyang Wang , Anurag Ranjan , Josh Susskind , Miguel Angel Bautista

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 models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility…

Biomolecules · Quantitative Biology 2024-12-30 Damiano Sgarbossa , Umberto Lupo , Anne-Florence Bitbol

Protein sequence design is a challenging problem in protein engineering, which aims to discover novel proteins with useful biological functions. Directed evolution is a widely-used approach for protein sequence design, which mimics the…

Machine Learning · Computer Science 2023-03-21 Chuanjiao Zong

Estimating three-dimensional conformations of a molecular graph allows insight into the molecule's biological and chemical functions. Fast generation of valid conformations is thus central to molecular modeling. Recent advances in…

Machine Learning · Computer Science 2025-02-18 Sohil Atul Shah , Vladlen Koltun

Understanding biological processes, drug development, and biotechnological advancements requires a detailed analysis of protein structures and functions, a task that is inherently complex and time-consuming in traditional protein research.…

Artificial Intelligence · Computer Science 2025-04-21 Yijia Xiao , Edward Sun , Yiqiao Jin , Qifan Wang , Wei Wang

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola

Flow matching is a recent framework to train generative models that exhibits impressive empirical performance while being relatively easier to train compared with diffusion-based models. Despite its advantageous properties, prior methods…

Computer Vision and Pattern Recognition · Computer Science 2023-07-18 Quan Dao , Hao Phung , Binh Nguyen , Anh Tran

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…

Current discriminative depth estimation methods often produce blurry artifacts, while generative approaches suffer from slow sampling due to curvatures in the noise-to-depth transport. Our method addresses these challenges by framing depth…

Computer Vision and Pattern Recognition · Computer Science 2024-12-20 Ming Gui , Johannes Schusterbauer , Ulrich Prestel , Pingchuan Ma , Dmytro Kotovenko , Olga Grebenkova , Stefan Andreas Baumann , Vincent Tao Hu , Björn Ommer

Spider silks are remarkable materials characterized by superb mechanical properties such as strength, extensibility and lightweightedness. Yet, to date, limited models are available to fully explore sequence-property relationships for…

Materials Science · Physics 2023-10-20 Wei Lu , David L. Kaplan , Markus J. Buehler

Unlike the predictable scaling laws in natural language processing and computer vision, protein language models (PLMs) scale poorly: for many tasks, models within the same family plateau or even decrease in performance, with mid-sized…

Machine Learning · Computer Science 2026-03-10 Darius Catrina , Christian Bepler , Samuel Sledzieski , Rohit Singh
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