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Cryo-Electron Microscopy (Cryo-EM) is a Nobel prize-winning technology for determining the 3D structure of particles at near-atomic resolution. A fundamental step in the recovering of the 3D single-particle structure is to align its 2D…

Image and Video Processing · Electrical Eng. & Systems 2021-01-12 Koby Bibas , Gili Weiss-Dicker , Dana Cohen , Noa Cahan , Hayit Greenspan

The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo-EM),…

Biological Physics · Physics 2017-11-17 Lars V. Bock , Michal H. Kolář , Helmut Grubmüller

Cryo-electron tomography (Cryo-ET) is a 3D imaging technique that enables the systemic study of shape, abundance, and distribution of macromolecular structures in single cells in near-atomic resolution. However, the systematic and efficient…

Biomolecules · Quantitative Biology 2021-06-29 Kai Yi , Jianye Pang , Yungeng Zhang , Xiangrui Zeng , Min Xu

Protein structure determination has long been one of the primary challenges of structural biology, to which deep machine learning (ML)-based approaches have increasingly been applied. However, these ML models generally do not incorporate…

Biological Physics · Physics 2025-11-14 Tom Pan , Evan Dramko , Mitchell D. Miller , Anastasios Kyrillidis , George N. Phillips

Cryo-electron tomography (cryo-ET) enables structural characterization of biomolecules under near-native conditions. Existing approaches for interpreting the resulting three-dimensional volumes are computationally expensive and have…

Quantitative Methods · Quantitative Biology 2025-10-28 Chengxuan Li , August George , Reece Neff , Doo Nam Kim , Trevor Moser , Kate Baldwin , Malio Nelson , Arsam Firoozfar , James E Evans , Margaret S Cheung

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

Integrative modeling of macromolecular assemblies allows for structural characterization of large assemblies that are recalcitrant to direct experimental observation. A Bayesian inference approach facilitates combining data from…

Biomolecules · Quantitative Biology 2026-01-13 Shreyas Arvindekar , Kartik Majila , Shruthi Viswanath

Proteins play crucial roles in every cellular process by interacting with each other, with nucleic acids, metabolites, and other molecules. The resulting assemblies can be very large and intricate and pose challenges to experimental…

Biomolecules · Quantitative Biology 2021-03-16 Charlotte W. van Noort , Rodrigo V. Honorato , Alexandre M. J. J. Bonvin

Recent breakthroughs in high-resolution imaging of biomolecules in solution with cryo-electron microscopy (cryo-EM) have unlocked new doors for the reconstruction of molecular volumes, thereby promising further advances in biology,…

Image and Video Processing · Electrical Eng. & Systems 2022-05-27 Claire Donnat , Axel Levy , Frederic Poitevin , Ellen Zhong , Nina Miolane

We describe a novel coarse-grained simulation method for modelling the dynamics of globular macromolecules, such as proteins. The macromolecule is treated as a continuum that is subject to thermal fluctuations. The model includes a…

Computational Physics · Physics 2015-06-11 Robin Oliver , Daniel J. Read , Oliver G. Harlen , Sarah A. Harris

Cryo-electron microscopy (cryo-EM) has become a tool of fundamental importance in structural biology, helping us understand the basic building blocks of life. The algorithmic challenge of cryo-EM is to jointly estimate the unknown 3D poses…

Computer Vision and Pattern Recognition · Computer Science 2022-09-01 Axel Levy , Frédéric Poitevin , Julien Martel , Youssef Nashed , Ariana Peck , Nina Miolane , Daniel Ratner , Mike Dunne , Gordon Wetzstein

After the recent ground-breaking advances in protein structure prediction, one of the remaining challenges in protein machine learning is to reliably predict distributions of structural states. Parametric models of fluctuations are…

Machine Learning · Computer Science 2024-01-25 Marloes Arts , Jes Frellsen , Wouter Boomsma

We introduce a novel class of Bayesian mixtures for normal linear regression models which incorporates a further Gaussian random component for the distribution of the predictor variables. The proposed cluster-weighted model aims to…

Methodology · Statistics 2026-05-26 Panagiotis Papastamoulis , Konstantinos Perrakis

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

Studying the conformations involved in the dimerization of cadherins is highly relevant to understand the development of tissue and its failure, which is associated with tumors and metastases. Experimental techniques, like X-ray…

Biomolecules · Quantitative Biology 2020-02-26 S. Terzoli , G. Tiana

Cryo-electron tomography enables 3D visualization of cells in a near native state at molecular resolution. The produced cellular tomograms contain detailed information about all macromolecular complexes, their structures, their abundances…

Quantitative Methods · Quantitative Biology 2019-04-30 Min Xu , Elitza I Tocheva , Yi-Wei Chang , Grant J Jensen , Frank Alber

Cryo-electron microscopy (cryo-EM) enables single-particle analysis of biological macromolecules under strict low-dose imaging conditions, but the resulting micrographs often exhibit extremely low signal-to-noise ratios and weak particle…

Computer Vision and Pattern Recognition · Computer Science 2026-04-21 Xiaoqi Wu , Xueying Zhan , Wen Li , Junhao Wu , Xin Huang , Min Xu

In cryo-electron microscopy (cryo-EM), a microscope generates a top view of a sample of randomly-oriented copies of a molecule. The problem of single particle reconstruction (SPR) from cryo-EM is to use the resulting set of noisy 2D…

Numerical Analysis · Mathematics 2014-09-16 Gene Katsevich , Alexander Katsevich , Amit Singer

Motivated by the task of 2-D classification in single particle reconstruction by cryo-electron microscopy (cryo-EM), we consider the problem of heterogeneous multireference alignment of images. In this problem, the goal is to estimate a…

Image and Video Processing · Electrical Eng. & Systems 2019-10-03 Chao Ma , Tamir Bendory , Nicolas Boumal , Fred Sigworth , Amit Singer

AI-based in silico methods have improved protein structure prediction but often struggle with large protein complexes (PCs) involving multiple interacting proteins due to missing 3D spatial cues. Experimental techniques like Cryo-EM are…

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