Barends, T.R.M. et al. Nature 10.1038/nature12773 (24 November 2013).

X-ray free-electron lasers (XFELs) provide very intense femtosecond X-ray pulses, allowing useable diffraction data to be collected from a stream of many thousands of tiny microcrystals before they are destroyed by radiation damage. This emerging approach, known as serial femtosecond crystallography, is proving to be very useful for determining structures of proteins that cannot be coaxed to form the large crystals necessary for conventional X-ray diffraction. To date, all protein structures solved using serial femtosecond crystallography have relied on a data analysis method known as molecular replacement, in which known related structures are used to obtain crystallographic phases for the new protein data. Barends et al. show that it is possible to borrow the method of heavy-atom doping from conventional crystallography. Heavy atoms intensify X-ray scattering and allow phases to be determined. This allowed them to solve the structure of lysozyme at 2.1 Å resolution without any prior structural knowledge.