Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Molecular insights into the dual-glycoprotein surface layer of the oral bacterium Tannerella serpentiformis.

Journal of molecular graphics & modelling·2026

Same author

Comparing isotherm parameter determination methods for hydrophobic interaction chromatography.

Journal of chromatography. A·2026

Same author

Navigating the Pre- and Post-AlphaFold Divide: CAPRI 8th Evaluation Meeting, February 12-14, Grenoble, FR.

Proteins·2025

Same author

Updates to the CASP Infrastructure in 2024.

Proteins·2025

Same author

Improved prediction of antibody and their complexes with clustered generative modelling ensembles.

Bioinformatics advances·2025

Same author

Biomolecular Interaction Prediction in the Pre- and Post-AlphaFold Era: The 8th CAPRI Evaluation.

Proteins·2025

Search research articles

Related Experiment Video

Updated: Oct 2, 2025

A Robust Single-Particle Cryo-Electron Microscopy cryo-EM Processing Workflow with cryoSPARC, RELION, and Scipion

A Robust Single-Particle Cryo-Electron Microscopy cryo-EM Processing Workflow with cryoSPARC, RELION, and Scipion

Published on: January 31, 2022

Interface refinement of low- to medium-resolution Cryo-EM complexes using HADDOCK2.4.

Tim Neijenhuis¹, Siri C van Keulen¹, Alexandre M J J Bonvin¹

¹Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Science for Life, Faculty of Science - Chemistry, Utrecht University, Padualaan 8, 3584 CH, Utrecht, the Netherlands.

Structure (London, England : 1993)

|February 26, 2022

Summary

This summary is machine-generated.

This study introduces a new computational method to fix atomic clashes in protein models derived from cryo-electron microscopy (cryo-EM) data. The approach significantly improves the accuracy of protein-protein interfaces (PPIs) in structural biology.

Keywords:

HADDOCK atomic clashes electron density map interface quality protein-protein interfaces refinement

More Related Videos

High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE

High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE

Published on: May 16, 2017

Routine Collection of High-Resolution cryo-EM Datasets Using 200 KV Transmission Electron Microscope

Routine Collection of High-Resolution cryo-EM Datasets Using 200 KV Transmission Electron Microscope

Published on: March 16, 2022

Related Experiment Videos

Last Updated: Oct 2, 2025

A Robust Single-Particle Cryo-Electron Microscopy cryo-EM Processing Workflow with cryoSPARC, RELION, and Scipion

A Robust Single-Particle Cryo-Electron Microscopy cryo-EM Processing Workflow with cryoSPARC, RELION, and Scipion

Published on: January 31, 2022

High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE

High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE

Published on: May 16, 2017

Routine Collection of High-Resolution cryo-EM Datasets Using 200 KV Transmission Electron Microscope

Routine Collection of High-Resolution cryo-EM Datasets Using 200 KV Transmission Electron Microscope

Published on: March 16, 2022

Area of Science:

Structural biology
Computational biology
Biophysics

Background:

Multimeric protein complexes are essential for cellular functions.
Cryo-electron microscopy (cryo-EM) provides structural insights into these complexes.
Low-resolution cryo-EM maps can lead to atomic clashes when fitting individual protein monomers, particularly at protein-protein interfaces (PPIs).

Purpose of the Study:

To develop and validate a computational refinement strategy to resolve atomic clashes at PPIs in cryo-EM structures.
To optimize intermolecular interactions within protein assemblies modeled from cryo-EM data.

Main Methods:

A refinement approach based on HADDOCK2.4 was employed.
Eight different refinement protocols were tested on a dataset of 14 cryo-EM complexes.
The best protocol involved semi-flexible simulated annealing with centroid restraints on monomers.

Main Results:

The optimized protocol reduced intermolecular atomic clashes by 98%.
The refinement did not significantly degrade the fit to the cryo-EM density map.
This method effectively addresses inaccuracies in protein-protein interfaces.

Conclusions:

A robust computational method for refining cryo-EM structures has been developed.
This approach enhances the accuracy of protein-protein interactions in structural models.
The method is valuable for improving the quality of atomic models from low- to medium-resolution cryo-EM data.