Electron cryo-microscopy (cryo-EM) reached single-atom resolution for 3D structure determination of biological macromolecules. Cryo-EM has been determining the structures of soluble as well as membrane proteins that have a key role in human diseases. It has become possible to obtain sufficiently high resolution structures to visualise water molecules, hydrogen atoms, bound drug molecules and in the cases of optimised samples, individual protein atoms. For protein structures, especially membrane proteins, improvements in resolution below 3 Å would mean improved rotamer assignments due to better defined side chain densities, visualisation of bound drug or ligand molecules and an unambiguous assignment of structurally ordered water molecules that are very important for any structure-based drug discovery.

The resolution leap is possible due to technological advances both in cryo-EM hardware and data processing software.

In this webinar Thermo Fisher Scientific will show how their 300 kV and 200 kV, cryo-transmission electron microscopes (Thermo Fisher Krios G4 and Glacios) equipped with Selectris Imaging Filter and Falcon 4i electron counting detector allows to inform structure-based drug discovery. They will also show many results on membrane protein structures as well as small sub-100 kDa proteins going beyond 2.5 Å resolution. 

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