A Shared Vision for Macromolecular Crystallography over the Next Five Years

Macromolecular crystallography (MX) is the dominant means of determining the three-dimensional structures of biological macromolecules, but the method has reached a critical juncture. New diffraction-limited storage rings and upgrades to the existing sources will provide beamlines with higher flux and brilliance, and even the largest detectors can collect at rates of several hundred hertz. Electron cryomicroscopy is successfully competing for structural biologists' most exciting projects. As a result, formerly scarce beam time is becoming increasingly abundant, and beamlines must innovate to attract users and ensure continued funding. Here, we will show how data collection has changed over the preceding five years and how alternative methods have emerged. We then explore how MX at synchrotrons might develop over the next five years. We predict that, despite the continued dominance of rotation crystallography, applications previously considered niche or experimental, such as serial crystallography, pink-beam crystallography, and crystallography at energies above 25 keV and below 5 keV, will rise in prominence as beamlines specialize to offer users the best value. Most of these emerging methods will require new hardware and software. With these advances, MX will more efficiently provide the high-resolution structures needed for drug development. MX will also be able to address a broader range of questions than before and contribute to a deeper understanding of biological processes in the context of integrative structural biology.