Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons

The authors show that serial millisecondcrystallography (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.