Structure determination based on continuous diffraction from macromolecular crystals

Bright and coherent X-ray sources, such free-electron lasers, have spurred large activities in developing new methods to obtain the structures of biological macromolecules. In particular, single-molecule diffraction is highly desired, as it would abolish the need for crystallization. It provides considerably more diffraction intensity information than needed to solve a structure, unlike crystal diffraction, which is usually insufficient for direct phasing. To overcome the challenge of weak scattering signals of single molecules, the direct phasing approaches in coherent diffractive imaging have been combined with crystals in several imaginative ways. One of these, using crystals with translational disorder, has been used to phase continuous femtosecond X-ray diffraction data from photosystem II complexes, offering a paradigm shift in crystallography.