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Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...

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Transmission electron microscopy (TEM) can be used to determine the 3D structure of biological samples with the help of techniques such as electron microscope tomography and single-particle reconstruction. While single-particle reconstruction can examine macromolecules and macromolecular complexes in vitro conditions only, tomography permits the study of cell components or small cells in vivo.
Electron Tomography
Electron tomography can be performed either in TEM or STEM (scanning transmission...

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Updated: Dec 25, 2025

Cryo-EM and Single-Particle Analysis with Scipion

Cryo-EM and Single-Particle Analysis with Scipion

Published on: May 29, 2021

Simulation-Based Methods for Model Building and Refinement in Cryoelectron Microscopy.

Thomas Dodd^1,2, Chunli Yan^1,2, Ivaylo Ivanov^1,2

¹Department of Chemistry, Georgia State University, Atlanta, Georgia 30302, United States.

Journal of Chemical Information and Modeling

|March 24, 2020

Summary

This summary is machine-generated.

This review covers molecular modeling for cryoelectron microscopy (cryo-EM), focusing on simulation methods like molecular dynamics flexible fitting (MDFF) to build accurate macromolecular models from density maps.

Keywords:

RNA polymerases cryoelectron microscopy de novo model building gene regulation hybrid methods molecular dynamics flexible fitting (MDFF)molecular modeling transcription preinitiation complexes

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Single Particle Cryo-Electron Microscopy: From Sample to Structure

Single Particle Cryo-Electron Microscopy: From Sample to Structure

Published on: May 29, 2021

Area of Science:

Structural Biology
Computational Biology
Biophysics

Background:

Cryoelectron microscopy (cryo-EM) has advanced structural biology.
Investigating large macromolecular assemblies requires accurate 3D models.
Flexible fitting methods are crucial for interpreting cryo-EM density maps.

Purpose of the Study:

To review modeling methods for flexible fitting in cryo-EM.
To highlight molecular simulation approaches, including molecular dynamics flexible fitting (MDFF).
To discuss hybrid modeling schemes and simulation workflows.

Main Methods:

Overview of modeling techniques for cryo-EM data.
Focus on atomistic molecular dynamics and Monte Carlo simulations.
Description of extensions to the molecular dynamics flexible fitting (MDFF) method.

Main Results:

Discussion of advantages, limitations, and alternatives to simulation-based methods.
Integration of model-building techniques into simulation workflows.
Illustrative examples using MDFF, cascade MDFF, and RosettaCM for transcription preinitiation complexes.

Conclusions:

MDFF and related simulation methods are powerful for modeling macromolecular assemblies.
Hybrid approaches enhance structural elucidation in cryo-EM.
Accurate models reveal functional insights into gene expression and regulation.