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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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Updated: May 15, 2026

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

Improving Protein Structure Prediction Using Integrative Cryo-EM and Ion Mobility Mass Spectrometry Modeling.

Jacob B Howard¹, Akshaya Narayanasamy², Steffen Lindert²

¹Department of Chemistry and Biochemistry, Ohio State University, Columbus, Ohio 43210, United States.

Journal of Chemical Theory and Computation

|May 14, 2026

Summary

This summary is machine-generated.

We developed CRIM, a new method combining cryo-electron microscopy (cryo-EM) and ion mobility mass spectrometry (IM-MS) to improve protein structure prediction accuracy, especially for challenging targets.

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A Protocol for Computer-Based Protein Structure and Function Prediction

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Last Updated: May 15, 2026

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

A Protocol for Computer-Based Protein Structure and Function Prediction

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Area of Science:

Structural biology
Computational biology
Biophysics

Background:

Accurate protein 3D structures are vital for understanding biological functions and for drug discovery.
High-resolution techniques like cryo-EM and X-ray crystallography provide detailed structures, but are not always applicable.
Low-resolution or sparse data, and methods like ion mobility mass spectrometry (IM-MS) provide complementary information but lack atomistic detail.

Purpose of the Study:

To develop an integrative scoring function that combines low-resolution cryo-electron microscopy (cryo-EM) data with ion mobility mass spectrometry (IM-MS) collisional cross section (CCS) restraints.
To enhance the accuracy of monomeric protein structure prediction, particularly when only sparse experimental data is available.

Main Methods:

Developed CRIM (cryo-EM + IM-MS), an integrative Rosetta scoring function.
CRIM integrates the REF2015 energy function with CCS agreement (PARCS) and an electron density term (elec_dens_fast).
Tested CRIM on ideal and experimental datasets of monomeric proteins, comparing its performance against established metrics and AlphaFold3.

Main Results:

CRIM significantly improved protein structure prediction accuracy on both ideal and experimental datasets.
On an ideal dataset (60 proteins), CRIM reduced mean RMSD from 3.65 to 2.90 Å and increased TM-score from 0.88 to 0.90.
On an experimental dataset (54 proteins), CRIM lowered mean RMSD from 6.65 to 4.38 Å and increased TM-score from 0.73 to 0.79.
CRIM demonstrated competitive performance against AlphaFold3, outperforming it on specific challenging cases.

Conclusions:

CRIM provides a practical and effective framework for integrating complementary cryo-EM and IM-MS data.
This integrative approach substantially improves monomeric protein structure prediction accuracy.
The CRIM score function is available in Rosetta, facilitating its use in structural biology research.