Extending the reach of single-particle cryoEM

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.