CHAPTER 3:Overcoming Data Processing Challenges for Breakthrough Crystallography

X-Ray free-electron laser (XFEL) sources have the potential to greatly enhance our understanding of biological macromolecules, by examining reactions and complexes with time resolution down to the femtosecond level, and under operational conditions. What is required from data processing is the ability to measure structure factor intensities from the Bragg spots in diffraction patterns, with similar accuracy to that achieved with synchrotron sources over the past four decades. However, the computational models that have been tremendously successful in reducing synchrotron-based data do not fully capture the complexity of XFEL experiments, owing in part to the nature of the exposures, which are still shots instead of rotational image series. Physical properties, including details of the crystals’ mosaic structure that have previously been obscure, influence the diffraction pattern and must be carefully modelled. Data quality metrics must be re-examined in light of these experimental differences, in service of the final goal of producing the best possible electron density maps from the observed measurements.