Cutting-edge structural biology research requires that molecular mechanisms are studied at conditions that mirror, as closely as possible, the functional in vivo state of the molecules. Until recently, researchers relied on X-ray crystallography for structural determination, but these samples are, by definition, taken out of their native environment during crystallization. Not only that, but crystallization is time-consuming, and the technique is not suitable for all samples because some proteins do not crystallize. (Large protein complexes in particular, despite providing great insight into native function, have been difficult to stabilize and crystallize.) To maintain molecular structures in their functional states, samples should be studied in solution, in their native hydrated environment, which is now possible with cryo-electron microscopy (cryo-EM).

With cryo-EM, structural biologists can not only study proteins and viruses in their biologically relevant forms, but they can also determine how these samples interact with other marker molecules or compounds. For example, they can observe the mechanism by which a virus enters a cell or membrane-embedded proteins that rely on their hydrophobic environment to dictate their structure and function. Size, complexity, and flexibility are no longer roadblocks towards high-resolution structural characterization.