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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…

We present a geometry-aware method for heterogeneous single-particle cryogenic electron microscopy (cryo-EM) reconstruction that predicts atomic backbone conformations. To incorporate protein-structure priors, we represent the backbone as a…

Computer Vision and Pattern Recognition · Computer Science 2026-03-09 Jonathan Krook , Axel Janson , Joakim Andén , Melanie Weber , Ozan Öktem

A single-particle cryo-electron microscopy (cryo-EM) measurement, called a micrograph, consists of multiple two-dimensional tomographic projections of a three-dimensional (3-D) molecular structure at unknown locations, taken under unknown…

Image and Video Processing · Electrical Eng. & Systems 2026-03-10 Shay Kreymer , Amit Singer , Tamir Bendory

Recent developments in deep learning-based methods demonstrated its potential to predict the 3D protein structures using inputs such as protein sequences, Cryo-Electron microscopy (Cryo-EM) images of proteins, etc. However, these methods…

Computer Vision and Pattern Recognition · Computer Science 2022-11-29 Jaydeep Rade , Soumik Sarkar , Anwesha Sarkar , Adarsh Krishnamurthy

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

Recent advancements in deep learning for predicting 3D protein structures have shown promise, particularly when leveraging inputs like protein sequences and Cryo-Electron microscopy (Cryo-EM) images. However, these techniques often fall…

Computer Vision and Pattern Recognition · Computer Science 2024-08-13 Jaydeep Rade , Ethan Herron , Soumik Sarkar , Anwesha Sarkar , Adarsh Krishnamurthy

The cryo-electron microscope (cryo-EM) is increasingly popular these years. It helps to uncover the biological structures and functions of macromolecules. In this paper, we address image denoising problem in cryo-EM. Denoising the cryo-EM…

Computation · Statistics 2018-10-26 Yin Xian , Hanlin Gu , Wei Wang , Xuhui Huang , Yuan Yao , Yang Wang , Jian-Feng Cai

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

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

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

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

Constructing atomic models from cryo-electron microscopy (cryo-EM) maps is a crucial yet intricate task in structural biology. While advancements in deep learning, such as convolutional neural networks (CNNs) and graph neural networks…

Quantitative Methods · Quantitative Biology 2024-11-01 Xin , Ma , Dong Si

Cryo-EM reconstruction algorithms seek to determine a molecule's 3D density map from a series of noisy, unlabeled 2D projection images captured with an electron microscope. Although reconstruction algorithms typically model the 3D volume as…

Biomolecules · Quantitative Biology 2021-07-06 Ellen D. Zhong , Adam Lerer , Joseph H. Davis , Bonnie Berger

Revealing the structure of complex biological macromolecules, such as proteins, is an essential step for understanding the chemical mechanisms that determine the diversity of their functions. Synchrotron based x-ray crystallography and…

Understanding complex biological macromolecules, especially proteins, is vital for grasping their diverse chemical functions with direct impact in biology and pharmacology. While techniques like X-ray crystallography and cryo-electron…

Biomolecules · Quantitative Biology 2024-04-12 S. H. Mejias , A. L. Cortajarena , R. Mincigrucci , C. Svetina , C. Masciovecchio

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

Cryo-EM is a transformational paradigm in molecular biology where computational methods are used to infer 3D molecular structure at atomic resolution from extremely noisy 2D electron microscope images. At the forefront of research is how to…

Quantitative Methods · Quantitative Biology 2025-06-12 Shayan Shekarforoush , David B. Lindell , Marcus A. Brubaker , David J. Fleet

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

Determining the structure of a protein has been a decades-long open question. A protein's three-dimensional structure often poses nontrivial computation costs, when classical simulation algorithms are utilized. Advances in the transformer…

Machine Learning · Computer Science 2023-10-09 Chen Dun , Qiutai Pan , Shikai Jin , Ria Stevens , Mitchell D. Miller , George N. Phillips, , Anastasios Kyrillidis

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