Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons
T. Weinert, N. Olieric, R. Cheng, S. Brünle et al.
The authors show that serial millisecond crystallography (SMX) at synchrotrons allows fast, straightforward structure determination at room-temperature for large soluble macromolecular complexes as well as membrane proteins. Using SMX, a much larger dose can be distributed over many crystals, resulting in higher resolution structures with less-radiation damage compared with classical room-temperature methods. Modern fast frame rate detectors produce results of excellent quality, making even native SAD phasing possible in less than a single 8-h synchrotron shift. Using ultra high frame rate detectors and next-generation diffraction-limited sources, time-resolved measurements in the micro- and perhaps nanosecond range may become possible at synchrotrons. Given the comparatively simple sample preparation, data collection, data processing and its great potential for automation, the authors believe that SMX is the method of choice for room-temperature structure determination and fragment screening approaches.
X-ray Free Electron Laser: Opportunities for drug discovery
Cheng R., Abela R., Hennig M.
The authors demonstrate that XFEL structure determination has matured to reality and point out the many advantages of the technology: Unmet brilliance and focus, femtosecond pulses and low/no radiation damage and measurement at room temperature allow structure determinations of challenging systems like membrane proteins, investigation of time-resolved ligand binding, new structural insights due to room temperature and full automation of crystal diffraction experiments.
Structural biology: doors open at the European XFEL
A technology feature by Nature Methods’ technology editor Vivien Marx about free electron lasers to comment on the opening of the European X-ray Free Electron Laser (EuXFEL) in Hamburg, Germany. One paragraph of the article refers to the SwissFEL (opened in December 2016) and the applied research at this instrument that will be facilitated by leadXpro AG.
Serial millisecond crystallography for routine room temperature structure determination at synchrotrons
Tobias Weinert, Natacha Olieric, Robert Cheng, Steffen Brünle, Daniel James, Dmitry Ozerov, Dardan Gashi, Laura Vera, May Marsh, Kathrin Jaeger, Florian Dworkowski, Ezequiel Panepucci, Shibom Basu, Petr Skopintsev, Andrew S. Doré, Tian Geng, Robert M. Cooke, Mengning Liang, Andrea E. Prota, Valerie Panneels, Przemyslaw Nogly, Ulrich Ermler, Gebhard Schertler, Michael Hennig, Michel O. Steinmetz, Meitian Wang & Jörg Standfuss
A publication co-authored by PSI, leadXpro and Heptares demonstrate the use of serial millisecond crystallography at a synchrotron beamline equipped with high-viscosity injector (LCP-injector) and high frame-rate detector (Eiger). This enables crystallographic experiments to be performed at room temperature – which is a crucial step towards structures under more physiological conditions. The comparison of GPCR membrane protein X-ray data measured at synchrotron and X-ray Free Electron Laser shows superiority of the XFEL structure quality.