X-ray crystallography is remarkably successful at yielding atomic-resolution structures of proteins and other biological molecules. But that success has relied on growing macroscopic crystals. The countless identical molecules arrayed in a crystal share a radiation dose orders of magnitude higher than any one of them could tolerate alone. Moreover, the interference of x rays elastically scattered from the molecules concentrates the scattering intensity in a set of Bragg peaks. The larger the crystal, the better the signal-to-noise ratio.
Unfortunately, many biomolecules, particularly the proteins responsible for cross-membrane communication, resist forming macroscopic crystals; some defy crystallization altogether. In 2000, Uppsala University's Janos Hajdu and colleagues simulated what would happen to a single uncrystallized protein or small assemblies of them placed in a hard x-ray beam from a free-electron laser (FEL).1 According to their model, photoionization would destroy a protein in a few tens of femtoseconds. Stripped of electrons, the protein...
