Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers

A computational approach and software tool, cctbx.xfel, enables the determination of accurate macromolecular structure factors using a relatively small number of serial femtosecond crystallography diffraction snapshots. X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract meaningful high-resolution signals from fewer diffraction measurements.