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Structural dynamics of macromolecules is critical to their structural-function relationship. Cryogenic electron microscopy (CryoEM) provides snapshots of vitrified protein at different compositional and conformational states, and the…

Quantitative Methods · Quantitative Biology 2026-01-27 Muyuan Chen , Muchen Li , Renjie Liao

Single-particle cryo-electron microscopy (cryo-EM) has recently joined X-ray crystallography and NMR spectroscopy as a high-resolution structural method for biological macromolecules. Cryo-EM was selected by Nature Methods as Method of the…

Computational Physics · Physics 2018-03-20 Amit Singer

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

In cryo-electron microscopy (EM), molecular structures are determined from large numbers of projection images of individual particles. To harness the full power of this single-molecule information, we use the Bayesian inference of EM…

Biomolecules · Quantitative Biology 2018-01-17 Pilar Cossio , David Rohr , Fabio Baruffa , Markus Rampp , Volker Lindenstruth , Gerhard Hummer

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

Single-particle cryo-Electron Microscopy (EM) has become a popular technique for determining the structure of challenging biomolecules that are inaccessible to other technologies. Recent advances in automation, both in data collection and…

Computer Vision and Pattern Recognition · Computer Science 2021-05-31 Ye Zhou , Amit Moscovich , Tamir Bendory , Alberto Bartesaghi

Single particle cryo-electron microscopy is a vital tool for 3D characterization of protein structures. A typical workflow involves acquiring projection images of a collection of randomly oriented particles, picking and classifying…

Image and Video Processing · Electrical Eng. & Systems 2021-03-22 S. V. Venkatakrishnan , Puneet Juneja , Hugh O'Neill

Cryo-EM data processing typically focuses on the structure of the main conformational state under investigation and discards images that belong to other states. This approach can reach atomic resolution, but ignores vast amounts of valuable…

Biomolecules · Quantitative Biology 2024-02-20 Felix Lambrecht , Andreas Kröpelin , Mario Lüttich , Michael Habeck , David Haselbach , Holger Stark

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

Laser flash melting and revitrification experiments have recently improved the time resolution of cryo-electron microscopy (cryo-EM) to the microsecond timescale, making it fast enough to observe many of the protein motions that are…

Instrumentation and Detectors · Physics 2026-05-19 Wyatt A. Curtis , Constantin R. Krüger , Axel P. Tracol Gavard , Jakub Wenz , Marcel Drabbels , Ulrich J. Lorenz

We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be…

Data Analysis, Statistics and Probability · Physics 2016-01-20 Gerhard Hummer , Jürgen Köfinger

Cryo-electron microscopy (EM) single particle reconstruction is an entirely general technique for 3D structure determination of macromolecular complexes. However, because the images are taken at low electron dose, it is extremely hard to…

Computer Vision and Pattern Recognition · Computer Science 2019-04-17 Yifeng Fan , Zhizhen Zhao

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

Understanding protein flexibility and its dynamic interactions with other molecules is essential for studying protein function. Although cryogenic electron microscopy(cryo-EM) provides an opportunity to observe macromolecular dynamics…

Computer Vision and Pattern Recognition · Computer Science 2026-02-03 Bintao He , Yiran Cheng , Hongjia Li , Xiang Gao , Xin Gao , Fa Zhang , Renmin Han

The growing role of data-driven approaches to scientific discovery has unveiled a large class of models that involve latent transformations with a rigid algebraic constraint. Three-dimensional molecule reconstruction in Cryo-Electron…

Information Theory · Computer Science 2019-06-04 Amelia Perry , Jonathan Weed , Afonso S. Bandeira , Philippe Rigollet , Amit Singer

Cryogenic electron microscopy (cryo-EM) provides images from different copies of the same biomolecule in arbitrary orientations. Here, we present an end-to-end unsupervised approach that learns individual particle orientations from cryo-EM…

Image and Video Processing · Electrical Eng. & Systems 2021-07-08 Youssef S. G. Nashed , Frederic Poitevin , Harshit Gupta , Geoffrey Woollard , Michael Kagan , Chuck Yoon , Daniel Ratner

Cryo-electron microscopy (cryo-EM) studies using single particle reconstruction is extensively used to reveal structural information of macromolecular complexes. Aiming at the highest achievable resolution, state of the art electron…

Computer Vision and Pattern Recognition · Computer Science 2020-05-04 Ramin Norousi , Stephan Wickles , Thomas Becker , Roland Beckmann , Volker J. Schmid , Achim Tresch

Achieving a comprehensive understanding of the behaviour of proteins is greatly facilitated by the knowledge of their structures, thermodynamics and dynamics. All this information can be provided in an effective manner in terms of…

Quantitative Methods · Quantitative Biology 2019-03-27 Massimiliano Bonomi , Michele Vendruscolo

Single particle electron cryomicroscopy (cryo-EM) allows for structures of proteins and protein complexes to be determined from images of non-crystalline specimens. Cryo-EM data analysis requires electron microscope images of randomly…

Instrumentation and Detectors · Physics 2015-11-23 Jianhua Zhao , Marcus A. Brubaker , Samir Benlekbir , John L. Rubinstein

Cryo-electron microscopy (cryo-EM) has recently emerged as a powerful tool for obtaining three-dimensional (3D) structures of biological macromolecules in native states. A minimum cryo-EM image data set for deriving a meaningful…

Applications · Statistics 2014-04-28 Ting-Li Chen , Dai-Ni Hsieh , Hung Hung , I-Ping Tu , Pei-Shien Wu , Yi-Ming Wu , Wei-Hau Chang , Su-Yun Huang