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It is becoming clear that traditional, single-structure models of proteins are insufficient for understanding their biological function. Here, we outline one method for inferring, from experiments, not only the most common structure a…

Biological Physics · Physics 2014-08-04 Thomas J. Lane , Christian R. Schwantes , Kyle A. Beauchamp , Vijay S. Pande

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…

Cryo-Electron Microscopy (cryo-EM) has emerged as a key technology to determine the structure of proteins, particularly large protein complexes and assemblies in recent years. A key challenge in cryo-EM data analysis is to automatically…

Biomolecules · Quantitative Biology 2023-04-04 Nabin Giri , Raj S. Roy , Jianlin Cheng

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

While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims…

Resolving the structural variability of proteins is often key to understanding the structure-function relationship of those macromolecular machines. Single particle analysis using Cryogenic electron microscopy (CryoEM), combined with…

Quantitative Methods · Quantitative Biology 2022-11-22 Muyuan Chen , Bogdan Toader , Roy Lederman

Integrative modeling enables structure determination for large macromolecular assemblies by combining data from multiple sources of experiment data with theoretical and computational predictions. Recent advancements in AI-based structure…

Biomolecules · Quantitative Biology 2025-01-24 Kartik Majila , Shreyas Arvindekar , Muskaan Jindal , Shruthi Viswanath

Protein structure prediction models are now capable of generating accurate 3D structural hypotheses from sequence alone. However, they routinely fail to capture the conformational diversity of dynamic biomolecular complexes, often requiring…

Machine Learning · Computer Science 2025-12-02 Rishwanth Raghu , Axel Levy , Gordon Wetzstein , Ellen D. Zhong

Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

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

The structure of proteins is essential for its function. The determination of protein structures is possible by experimental or predicted by computational methods, but also a combination of both approaches is possible. Here, first an…

Other Quantitative Biology · Quantitative Biology 2020-03-03 Gerhard Mayer

Cryo-electron microscopy can now routinely deliver atomic resolution structures for a variety of biological systems. The relevance and value of these structures is directly related to their ability to help rationalize experimental…

Cryo-electron tomography (cryo-ET) has emerged as a powerful tool for studying the structural heterogeneity of proteins and their complexes, offering insights into macromolecular dynamics directly within cells. Driven by recent…

Biomolecules · Quantitative Biology 2025-07-01 Jackson Carrion , Joseph H. Davis

Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well…

Quantitative Methods · Quantitative Biology 2019-01-24 Thomas Löhr , Carlo Camilloni , Massimiliano Bonomi , Michele Vendruscolo

Throughout the history of electron microscopy, ribosomes have served as an ideal subject for imaging and technological development, which in turn has driven our understanding of ribosomal biology. Here, we provide a historical perspective…

Biomolecules · Quantitative Biology 2023-08-31 Samantha M. Webster , Mira B. May , Barrett M. Powell , Joseph H. Davis

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-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

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…

Biomolecules · Quantitative Biology 2021-12-13 F. Emil Thomasen , Kresten Lindorff-Larsen

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structure of proteins and other macromolecular complexes at near-atomic resolution. In single particle cryo-EM, the central problem is to reconstruct the…

Quantitative Methods · Quantitative Biology 2020-02-18 Ellen D. Zhong , Tristan Bepler , Joseph H. Davis , Bonnie Berger
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