Extending the reach of single-particle cryoEM
Ardan Patwardhan, Richard A. Henderson, Christopher J. Russo
Abstract
Molecular structure determination using electron cryomicroscopy (cryoEM) is poised in early 2025 to surpass X-ray crystallography as the most used method for experimentally determining new structures. But the technique has not reached the physical limits set by radiation damage and the signal-to-noise ratio in individual images of molecules. By examining these limits and comparing the number and resolution of structures determined versus molecular weight, we identify opportunities for extending the application of single-particle cryoEM. This will help guide technology development to continue the exponential growth of structural biology. • A decade after the resolution revolution, single-particle cryoEM is reviewed. • Limitations of cryoEM for structure determination are considered and compared to other methods. • Potential new technologies to continue the exponential growth of the field are discussed.