David Clark, PhD

What's Hot in 2021: Cryo-EM

This rapidly expanding tool is changing the face of drug discovery

My hot topic for 2021 is actually very cold! I wrote an overview of cryogenic electron microscopy (Cryo-What's Hot logoEM) for Eureka back in 2018 , and the technique has continued to go from strength to strength. Shown above is a cryo-EM structure of Dengue virus strain (green) complexed with human antibody (brown and violet).  Most recently, Cryo-EM has once again made the front cover of the prestigious science journal Nature because of the reports of three atomic resolution structures obtained using the technique.

The significance of this achievement is that this brings structures from cryo-EM into the same resolution range as those more routinely achieved using X-ray crystallography. Two independent groups have reported cryo-EM structures of the protein apoferritin at resolutions of 1.22 and 1.24 Angstroms, respectively. Of more direct relevance for drug design is the report of a structure of the GABA-A receptor (the target for benzodiazepine drugs) solved at 1.7 Angstroms. This is a considerable advance on the cryo-EM structure of the same protein reported in 2018, which only reached a resolution of 3.9 Angstroms.

Based on these very recently reported results, it seems likely that 2021 will bring further cryo-EM structures at similarly high resolutions that will provide important new insights for drug discovery projects.

--David Clark, PhD, Charles River Early Discovery