The Rise of Cryo-EM
One of the greatest advantages of cryo-EM relative to conventional structural biology techniques is its ability to analyze large, complex and flexible structures. Oftentimes these cannot be crystallized for X-ray crystallography (XRD) or are too large and complex for nuclear magnetic resonance (NMR) spectroscopy. These include many biologically important proteins, especially those with variable or flexible structures like membrane proteins. The established methods for structure determination, XRD and NMR, are now routinely integrated with cryo-EM density maps to achieve atomic-resolution models of complex, dynamic molecular assemblies.
Since the first model based on cryo-EM reconstruction was deposited with the PDB (Protein Data Bank) in 1997, the number of deposited structures has grown exponentially. Cryo-EM was responsible for entries to the EMDB surpassing 1,000 in 2016, with a quarter of all entries deposited that year alone. Many of these most recent depositions include critical macromolecular assemblies previously thought impervious to structure determination.