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Cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing to reconstruct 3D biomolecular structures up to near-atomic resolution. However, the 3D reconstruction process remains challenging, as the 3D structures…

Computer Vision and Pattern Recognition · Computer Science 2023-07-18 Bongjin Koo , Julien Martel , Ariana Peck , Axel Levy , Frédéric Poitevin , Nina Miolane

The three-dimensional structure of proteins plays a crucial role in determining their function. Protein structure prediction methods, like AlphaFold, offer rapid access to a protein structure. However, large protein complexes cannot be…

Biomolecules · Quantitative Biology 2025-03-05 Gabriel Ducrocq , Lukas Grunewald , Sebastian Westenhoff , Fredrik Lindsten

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

Single-particle cryo-EM has transformed structural biology but still faces challenges in resolving conformational heterogeneity at atomic resolution. Existing cryo-EM heterogeneity analysis methods either lack atomic details or tend to…

Biomolecules · Quantitative Biology 2025-10-21 Chengwei Zhang , Shimian Li , Yihao Niu , Zhen Zhu , Sihao Yuan , Sirui Liu , Yi Qin Gao

Assembly of protein complexes like virus shells, the centriole, the nuclear pore complex or the actin cytoskeleton is strongly determined by their spatial structure. Moreover it is becoming increasingly clear that the reversible nature of…

Subcellular Processes · Quantitative Biology 2014-05-13 Heinrich C. R. Klein , Ulrich S. Schwarz

Investigation of dynamic processes in cell biology very often relies on the observation in two dimensions of 3D biological processes. Consequently, the data are partial and statistical methods and models are required to recover the…

Applications · Statistics 2020-10-21 Yunjiao Lu , Pierre Hodara , Charles Kervrann , Alain Trubuil

Single-particle electron cryomicroscopy (cryo-EM) is an increasingly popular technique for elucidating the three-dimensional structure of proteins and other biologically significant complexes at near-atomic resolution. It is an imaging…

Computational Physics · Physics 2020-04-01 Amit Singer , Fred J. Sigworth

We address recovery of the three-dimensional backbone structure of single polypeptide proteins from single-particle cryo-electron microscopy (Cryo-SPA) data. Cryo-SPA produces noisy tomographic projections of electrostatic potentials of…

Biomolecules · Quantitative Biology 2024-10-02 Erik Jansson , Jonathan Krook , Klas Modin , Ozan Öktem

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

Proteins typically undergo conformational dynamics on the microsecond to millisecond timescale as they perform their function, which is much faster than the time-resolution of cryo-electron microscopy and has thus prevented real-time…

Biological Physics · Physics 2021-07-07 Jonathan M. Voss , Oliver F. Harder , Pavel K. Olshin , Marcel Drabbels , Ulrich J. Lorenz

In living cells, proteins involved in specialized biochemical functions are often spatially organized within biomolecular condensates. Increasing evidence suggests that some of these condensates, including DNA repair condensates, emerge…

Soft Condensed Matter · Physics 2026-05-15 Léa Beaulès , Judith Miné-Hattab , Pierre Illien , Vincent Dahirel

Simulations of macromolecular diffusion and adsorption in confined environments can offer valuable mechanistic insights into numerous biophysical processes. In order to model solutes at atomic detail on relevant time scales, Brownian…

Soft Condensed Matter · Physics 2021-03-16 Martin Reinhardt , Neil J. Bruce , Daria B. Kokh , Rebecca C. Wade

The folding and structure of biomacromolecules depend on the 3D distributions of their constituents, which ultimately controls their functionalities and interactions with other biomacromolecules. Atom probe tomography (APT) with its…

The mode of action of proteins is to a large extent given by their ability to adopt different conformations. This is why imaging single biomolecules at atomic resolution is one of the ultimate goals of biophysics and structural biology. The…

Biological Physics · Physics 2012-09-27 Jean-Nicolas Longchamp , Tatiana Latychevskaia , Conrad Escher , Hans-Werner Fink

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

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

Diffusion coefficient measurements are important for many biological and material investigations, such as particle dynamics, kinetics, and size determinations. Amongst current measurement methods, single particle tracking (SPT) offers the…

Biomolecules · Quantitative Biology 2011-07-12 Shannon Kian Zareh , Michael C. DeSantis , Jonathan Kessler , Je-Luen Li , Y. M. Wang

The coarse-grained molecular dynamics (MD) or Brownian dynamics (BD) simulation is a particle-based approach that has been applied to a wide range of biological problems that involve interactions with surrounding fluid molecules or the…

Soft Condensed Matter · Physics 2014-11-20 Szu-Pei Fu , Yuan-Nan Young , Shidong Jiang

Cryogenic electron microscopy is widely used in structural biology, but its resolution is often limited by the dynamics of the macromolecule. Here, we developed a refinement protocol based on Gaussian mixture models that integrates particle…

Quantitative Methods · Quantitative Biology 2023-08-31 Muyuan Chen , Michael F. Schmid , Wah Chiu

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…

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