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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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Related Experiment Video

Updated: Jan 1, 2026

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

Fragment-based drug discovery using cryo-EM.

Michael Saur¹, Michael J Hartshorn², Jing Dong¹

¹Astex Pharmaceuticals, 436 Cambridge Science Park, Cambridge, CB4 0QA, UK.

Drug Discovery Today

|December 27, 2019

Summary

This summary is machine-generated.

Electron cryo-microscopy (cryo-EM) now offers high-resolution structures suitable for drug discovery. This review shows cryo-EM is reproducible and efficient for fragment-based drug discovery (FBDD).

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Area of Science:

Structural Biology
Biochemistry
Drug Discovery

Background:

Recent advances in electron cryo-microscopy (cryo-EM) have significantly improved resolution capabilities.
High-resolution structures are increasingly valuable for drug discovery applications.

Purpose of the Study:

To review the application of cryo-EM in fragment-based drug discovery (FBDD).
To assess the suitability of in-house developed cryo-EM methods for FBDD.

Main Methods:

Review of in-house method development for cryo-EM.
Application of cryo-EM for structure determination in FBDD.
Utilizing β-galactosidase (Bgal) and pyruvate kinase 2 (PKM2) as test systems.

Main Results:

Cryo-EM can resolve molecular interactions between drug fragments and protein targets.
Current cryo-EM methods demonstrate sufficient reproducibility, quality, and throughput for FBDD.
Successful application demonstrated using Bgal and PKM2 systems.

Conclusions:

Cryo-EM is a viable and powerful tool for fragment-based drug discovery.
The technical capabilities of cryo-EM align with the demands of modern drug discovery pipelines.