# Enabling HighThroughput Electron Cryo-microscopy for Drug Discovery

**Authors:** Pamela A Williams

PMC · DOI: 10.1063/4.0000881 · 2025-10-27

## TL;DR

This paper discusses how cryo-EM is becoming a valuable tool in drug discovery by providing high-resolution protein-ligand structures when traditional methods fail.

## Contribution

The paper highlights recent advances in cryo-EM and its practical application in drug development at Astex.

## Key findings

- Cryo-EM is increasingly used for proteins that resist crystallization.
- Astex applies cryo-EM to support structure and fragment-based drug discovery.
- Further developments are needed to fully realize cryo-EM's potential in drug discovery.

## Abstract

Structure and fragment based drug discovery campaigns (SBDD and FBDD) rely on frequent access to high resolution protein-ligand structures, in order to support the design-make-test-analyse cycle. Protein crystallography is widely used to support such medicinal chemistry campaigns, but in recent years electron cryo-microscopy (cryo-EM) has emerged as alternative approach that may be applied to proteins that are recalcitrant to crystallisation. In this talk I will describe the advances that have enabled this, provide an illustration of how Astex uses cryo-EM to support drug development and reflect upon the additional developments that will be required if cryo-EM is to reach its full potential in both SBDD and FBDD.

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Source: https://tomesphere.com/paper/PMC12585770