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Related Experiment Video

Updated: Apr 11, 2026

$Microcrystal Electron Diffraction of Small Molecules$

Microcrystal Electron Diffraction of Small Molecules

Published on: March 15, 2021

High-throughput automated molecular replacement for small-molecule MicroED data.

Adam Thibodeaux¹, Guanhong Bu¹, Lael C Edwards¹

¹Department of Chemistry, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA.

|April 10, 2026

Summary

This summary is machine-generated.

Electron diffraction (ED) is gaining traction for molecular structure determination. A new automated molecular replacement method successfully solved a challenging small molecule structure, overcoming limitations of traditional ab initio phasing techniques.

Keywords:

3DED MicroED automation algorithms electron crystallography high-throughput methods molecular replacement small-molecule electron diffraction

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Last Updated: Apr 11, 2026

$Microcrystal Electron Diffraction of Small Molecules$

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Published on: March 15, 2021

$Microfluidic Chips for In Situ Crystal X-ray Diffraction and In Situ Dynamic Light Scattering for Serial Crystallography$

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Published on: April 24, 2018

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Published on: March 3, 2021

Area of Science:

Crystallography and structural biology
Electron diffraction (ED) applications
Small molecule structure determination

Background:

Electron diffraction (ED) is increasingly used for protein and small molecule structural characterization.
Ab initio phasing is standard for small molecules but struggles with radiation damage and poor crystallinity.
Molecular replacement (MR) is common for proteins but limited for small molecules due to challenges in generating conformations.

Purpose of the Study:

To develop a high-throughput automated molecular replacement (MR) workflow for electron diffraction (ED) data.
To solve the novel ED structure of corilagin, a pharmaceutically relevant macrocyclic gallotannin.
To validate the MR workflow against known macrocyclic structures at various resolutions.

Main Methods:

Development of a high-throughput automated molecular replacement workflow.
Application of the workflow to solve the ED structure of corilagin.
Validation using three known macrocycles (paritaprevir-α, paritaprevir-β, grazoprevir) at resolutions from 1.0 to 2.0 Å.

Main Results:

Successfully solved the novel ED structure of corilagin, which was intractable with ab initio phasing.
The automated MR workflow achieved successful solutions for all validation structures across tested resolutions.
Obtained R factors and RMSD values within acceptable limits compared to ab initio solved structures.

Conclusions:

The developed automated MR workflow is effective for solving small molecule ED structures, especially challenging ones.
This method overcomes limitations of ab initio phasing in electron diffraction.
The workflow demonstrates broad applicability for structural determination of macrocyclic compounds using ED data.