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Discovery
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David Clark, PhD

Art of the Science: Cryo-EM

High resolution cryo-EM structures provide new insights for drug discovery projects

What are we looking at?

This is an image of a structure of the human β3 GABAA receptor homopentamer solved to atomic resolution by cryo-electron microscopy (cryo-EM). It was published in Nature in 2020 ( https://www.nature.com/articles/s41586-020-2829-0 ).

How was the image generated?

The 3-D coordinates were obtained from the Protein Data Bank ( https://www.rcsb.org/structure/7a5v ) and the image was created on a Dell laptop running Windows 10 and using the Maestro molecular modelling software produced by Schrödinger ( https://www.schrodinger.com/products/maestro ).

What are researchers learning from this image?

This is one of the first protein structures solved by cryo-EM to a resolution equivalent to that normally only attained by traditional X-ray crystallography. As such, it represents a significant advance in science and technology. The GABAA receptor family contains important targets for the discovery and development of drugs for CNS disorders and high-resolution structures, such as this, will facilitate structure-based drug design and hopefully expedite the discovery of new therapeutics in due course.

Something cool about my lab?

At present, it’s in my home office. Molecular modelling can be done anywhere nowadays with a laptop and a broadband connection!