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We describe a new generation of algorithms capable of mapping the structure and conformations of macromolecules and their complexes from large ensembles of heterogeneous snapshots, and demonstrate the feasibility of determining both…

Biological Physics · Physics 2014-04-30 P. Schwander , R. Fung , A. Ourmazd

Single-particle cryo-electron microscopy (cryo-EM) is an emerging imaging modality capable of visualizing proteins and macro-molecular complexes at near-atomic resolution. The low electron-doses used to prevent sample radiation damage,…

Image and Video Processing · Electrical Eng. & Systems 2020-11-24 Qinwen Huang , Ye Zhou , Xiaochen Du , Reed Chen , Jianyou Wang , Cynthia Rudin , Alberto Bartesaghi

Single-particle cryo-electron microscopy (cryo-EM) has recently joined X-ray crystallography and NMR spectroscopy as a high-resolution structural method to resolve biological macromolecules. In a cryo-EM experiment, the microscope produces…

Information Theory · Computer Science 2022-10-28 Tamir Bendory , Nicolas Boumal , William Leeb , Eitan Levin , Amit Singer

Classifying structural variability in noisy projections of biological macromolecules is a central problem in Cryo-EM. In this work, we build on a previous method for estimating the covariance matrix of the three-dimensional structure…

Computer Vision and Pattern Recognition · Computer Science 2015-12-08 Joakim Andén , Eugene Katsevich , Amit Singer

Single particle cryogenic electron microscopy (cryo-EM) is an imaging technique capable of recovering the high-resolution 3-D structure of biological macromolecules from many noisy and randomly oriented projection images. One notable…

Biomolecules · Quantitative Biology 2024-01-30 Andy Zhang , Oscar Mickelin , Joe Kileel , Eric J. Verbeke , Nicholas F. Marshall , Marc Aurèle Gilles , Amit Singer

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling near-atomic-level visualization of biomolecular assemblies. However, the exponential growth in cryo-EM data throughput and complexity, coupled with diverse…

Quantitative Methods · Quantitative Biology 2026-02-25 Weining Fu , Kai Shu , Kui Xu , Qiangfeng Cliff Zhang

Cryo-electron microscopy (cryo-EM) emerges as a pivotal technology for determining the architecture of cells, viruses, and protein assemblies at near-atomic resolution. Traditional particle picking, a key step in cryo-EM, struggles with…

Biomolecules · Quantitative Biology 2024-04-17 Chentianye Xu , Xueying Zhan , Min Xu

Knowledge of a protein's atomic conformational ensemble is critical to determining its function, yet state-of-the-art ensemble prediction models are limited by lack of high-quality conformational data from simulation or experiment. Recent…

Machine Learning · Computer Science 2026-05-12 Jay Shenoy , Miro Astore , Axel Levy , Frédéric Poitevin , Sonya M. Hanson , Gordon Wetzstein

Cryogenic electron microscopy (Cryo-EM) has become an essential tool for capturing high-resolution biological structures. Despite its advantage in visualizations, the large storage size of Cryo-EM data file poses significant challenges for…

Machine Learning · Computer Science 2025-12-16 Chunyu Zou

Cryo-electron microscopy (cryo-EM) is a technique for reconstructing the 3-dimensional (3D) structure of biomolecules (especially large protein complexes and molecular assemblies). As the resolution increases to the near-atomic scale,…

Computer Vision and Pattern Recognition · Computer Science 2023-08-08 Weijie Chen , Xinyan Wang , Yuhang Wang

Cryo-electron microscopy (cryo-EM) is an indispensable technique for determining the 3D structures of dynamic biomolecular complexes. While typically applied to image a single molecular species, cryo-EM has the potential for structure…

Computer Vision and Pattern Recognition · Computer Science 2026-03-23 Jeffrey Gu , Minkyu Jeon , Ambri Ma , Serena Yeung-Levy , Ellen D. Zhong

We present a machine learning framework for modeling protein dynamics. Our approach uses L1-regularized, reversible hidden Markov models to understand large protein datasets generated via molecular dynamics simulations. Our model is…

Biomolecules · Quantitative Biology 2014-05-08 Robert T. McGibbon , Bharath Ramsundar , Mohammad M. Sultan , Gert Kiss , Vijay S. Pande

Constructing of molecular structural models from Cryo-Electron Microscopy (Cryo-EM) density volumes is the critical last step of structure determination by Cryo-EM technologies. Methods have evolved from manual construction by structural…

Machine Learning · Computer Science 2019-02-13 Kui Xu , Zhe Wang , Jiangping Shi , Hongsheng Li , Qiangfeng Cliff Zhang

We consider the problem of recovering the three-dimensional atomic structure of a flexible macromolecule from a heterogeneous cryo-EM dataset. The dataset contains noisy tomographic projections of the electrostatic potential of the…

Image and Video Processing · Electrical Eng. & Systems 2023-02-08 Carlos Esteve-Yagüe , Willem Diepeveen , Ozan Öktem , Carola-Bibiane Schönlieb

In recent years, an abundance of new molecular structures have been elucidated using cryo-electron microscopy (cryo-EM), largely due to advances in hardware technology and data processing techniques. Owing to these new exciting…

Information Theory · Computer Science 2020-04-22 Tamir Bendory , Alberto Bartesaghi , Amit Singer

Understanding sub-cellular protein localisation is an essential component to analyse context specific protein function. Recent advances in quantitative mass-spectrometry (MS) have led to high resolution mapping of thousands of proteins to…

Applications · Statistics 2019-03-12 Oliver M. Crook , Kathryn S. Lilley , Laurent Gatto , Paul D. W. Kirk

Cryogenic electron microscopy (cryo-EM) is an invaluable technique for determining high-resolution three-dimensional structures of biological macromolecules using transmission particle images. The inherent symmetry in these macromolecules…

Optimization and Control · Mathematics 2024-11-06 Qi Zhang , Chenglong Bao , Hai Lin , Mingxu Hu

The field of cryo-electron microscopy has made astounding advancements in the past few years, mainly due to advancements in electron detectors' technology. Yet, one of the key open challenges of the field remains the processing of…

Computer Vision and Pattern Recognition · Computer Science 2019-10-04 Yariv Aizenbud , Yoel Shkolnisky

Cryo-Electron Microscopy (cryo-EM) has become an extremely powerful method for resolving structural details of large biomolecular complexes. However, challenging problems in single-particle methods remain open because of (1) the low…

Biomolecules · Quantitative Biology 2019-08-12 Shengnan Lyu , Christian Wülker , Yuqing Pan , Amitesh S. Jayaraman , Jianhao Zheng , Yilin Cai , Gregory S. Chirikjian

Single particle cryo-electron microscopy has become a critical tool in structural biology over the last decade, able to achieve atomic scale resolution in three dimensional models from hundreds of thousands of (noisy) two-dimensional…

Numerical Analysis · Mathematics 2023-07-19 Aaditya V. Rangan , Leslie Greengard