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We introduce DiffFit, a differentiable algorithm for fitting protein atomistic structures into an experimental reconstructed Cryo-Electron Microscopy (cryo-EM) volume map. In structural biology, this process is necessary to…

Quantitative Methods · Quantitative Biology 2025-01-09 Deng Luo , Zainab Alsuwaykit , Dawar Khan , Ondřej Strnad , Tobias Isenberg , Ivan Viola

Physical imaging is a foundational characterization method in areas from condensed matter physics and chemistry to astronomy and spans length scales from atomic to universe. Images encapsulate crucial data regarding atomic bonding,…

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

Advances in imagery at atomic and near-atomic resolution, such as cryogenic electron microscopy (cryo-EM), have led to an influx of high resolution images of proteins and other macromolecular structures to data banks worldwide. Producing a…

Quantitative Methods · Quantitative Biology 2021-04-06 Nathan Ranno , Dong Si

Cryo-electron microscopy (cryo-EM) is an imaging modality that provides unique insights into the dynamics of proteins and other building blocks of life. The algorithmic challenge of jointly estimating the poses, 3D structure, and…

Computer Vision and Pattern Recognition · Computer Science 2022-10-17 Axel Levy , Gordon Wetzstein , Julien Martel , Frederic Poitevin , Ellen D. Zhong

Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature, it has the potential to provide…

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining high-resolution 3D biomolecular structures from imaging data. Its unique ability to capture structural variability has spurred the development of heterogeneous…

Computer Vision and Pattern Recognition · Computer Science 2025-01-17 Minkyu Jeon , Rishwanth Raghu , Miro Astore , Geoffrey Woollard , Ryan Feathers , Alkin Kaz , Sonya M. Hanson , Pilar Cossio , Ellen D. Zhong

Cryo-electron microscopy (cryo-EM) is a powerful technique in structural biology and drug discovery, enabling the study of biomolecules at high resolution. Significant advancements by structural biologists using cryo-EM have led to the…

Biomolecules · Quantitative Biology 2024-12-05 Yi Zhou , Yilai Li , Jing Yuan , Quanquan Gu

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. CryoEM provides direct visualization of individual macromolecules sampling different conformational and compositional states.…

Biomolecules · Quantitative Biology 2021-08-04 Muyuan Chen , Steven Ludtke

In the past decade, deep conditional generative models have revolutionized the generation of realistic images, extending their application from entertainment to scientific domains. Single-particle cryo-electron microscopy (cryo-EM) is…

Computer Vision and Pattern Recognition · Computer Science 2024-10-01 Jiakai Zhang , Qihe Chen , Yan Zeng , Wenyuan Gao , Xuming He , Zhijie Liu , Jingyi Yu

In single-particle cryo-electron microscopy (cryo-EM), the efficient determination of orientation parameters for 2D projection images poses a significant challenge yet is crucial for reconstructing 3D structures. This task is complicated by…

Image and Video Processing · Electrical Eng. & Systems 2025-09-30 Szu-Chi Chung

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

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

Recent advances in scanning tunneling and transmission electron microscopies (STM and STEM) have allowed routine generation of large volumes of imaging data containing information on the structure and functionality of materials. The…

Disordered Systems and Neural Networks · Physics 2021-06-24 Maxim Ziatdinov , Chun Yin Wong , Sergei V. Kalinin

Cryo-electron microscopy (cryo-EM) has emerged as a powerful technique for resolving the three-dimensional structures of macromolecules. A key challenge in cryo-EM is characterizing continuous heterogeneity, where molecules adopt a…

Machine Learning · Statistics 2026-02-20 Roey Yadgar , Roy R. Lederman , Yoel Shkolnisky

Cryo-electron tomography (Cryo-ET) is a powerful tool in structural biology for 3D visualization of cells and biological systems at resolutions sufficient to identify individual proteins in situ. The measurements are collected by tilting…

Signal Processing · Electrical Eng. & Systems 2025-09-03 Vinith Kishore , Valentin Debarnot , AmirEhsan Khorashadizadeh , Ivan Dokmanić

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

Cryo-electron microscopy (cryo-EM) remains pivotal in structural biology, yet the task of protein particle picking, integral for 3D protein structure construction, is laden with manual inefficiencies. While recent AI tools such as Topaz and…

Computer Vision and Pattern Recognition · Computer Science 2023-11-29 Fei He , Zhiyuan Yang , Mingyue Gao , Biplab Poudel , Newgin Sam Ebin Sam Dhas , Rajan Gyawali , Ashwin Dhakal , Jianlin Cheng , Dong Xu

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

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