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Related Experiment Video

Updated: Nov 11, 2025

Microcrystal Electron Diffraction of Small Molecules
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Microcrystal Electron Diffraction of Small Molecules.

Michael W Martynowycz1, Tamir Gonen2

  • 1Howard Hughes Medical Institute, University of California Los Angeles; Department of Biological Chemistry, University of California Los Angeles.

Journal of Visualized Experiments : Jove
|March 29, 2021
PubMed
Summary
This summary is machine-generated.

This study details a rapid protocol for preparing small molecule samples for Microcrystal Electron Diffraction (MicroED) using standard cryo-electron microscopy equipment. The method, demonstrated with carbamazepine, takes under 30 minutes for grid preparation.

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Area of Science:

  • Crystallography
  • Electron Microscopy
  • Drug Discovery

Background:

  • Microcrystal Electron Diffraction (MicroED) enables high-resolution structure determination of small molecules and proteins.
  • Standard electron cryo-microscopy (cryo-EM) equipment can be utilized for MicroED experiments.
  • Efficient sample preparation is crucial for successful MicroED analysis.

Purpose of the Study:

  • To present a detailed and rapid protocol for preparing small molecule samples for MicroED.
  • To demonstrate the protocol using a pharmaceutical compound, carbamazepine.
  • To provide guidelines for screening and data collection in MicroED experiments.

Main Methods:

  • Development of a streamlined protocol for preparing MicroED grids from small molecule samples.
  • Utilizing standard cryo-EM sample preparation techniques.
  • Demonstration with carbamazepine, a pharmaceutical agent.

Main Results:

  • A reproducible method for small molecule grid preparation for MicroED was established.
  • The entire sample preparation process, including screening and data collection, can be completed in under 30 minutes.
  • The protocol is applicable to small-molecule pharmaceuticals.

Conclusions:

  • The described protocol offers a fast and efficient method for MicroED sample preparation.
  • This technique facilitates the structural elucidation of small molecules using accessible cryo-EM instrumentation.
  • The rapid preparation time enhances the throughput for small molecule structure determination via MicroED.