Development of instrumentation and methods for MAD and structural genomics at the SRS, ESRF, CHESS and Elettra facilities

The evolution of the brilliance of synchrotron radiation sources has allowed combined functionalities of beamline optics for simultaneous high intensity, rapid tunability and narrow wavelength bandpass. This then combines the chance to measure protein crystal diffraction data at multiple wavelengths for optimized anomalous dispersion (MAD) differences for phasing as well as at high diffraction resolution from macromolecular structures and their complexes. Rapid de novo protein structure determination is now achieved. The selenomethionine substitution method offers a definite way to incorporate anomalous scattering atoms in a protein for MAD, although MAD is also a very versatile approach applicable to metalloproteins and to cases of many heavy atoms found useful in isomorphous derivative preparation (especially utilization of non‐isomorphous derivatives). Detector developments, especially image‐plate scanners and now CCDs, have revolutionized diffraction data quality and speed of data acquisition, with further developments, such as the pixel detector, in store. Cryocooling of the sample has greatly alleviated radiation damage problems. Computer hardware capabilities have also changed incredibly. Coordinated software developments for protein crystallography have been achieved [Collaborative Computational Project, Number 4 (1994). Acta Cryst. D50, 760–763]. Protein crystallography and synchrotron radiation is capable of yielding `genome level' numbers of protein structures. Results and capabilities are presented and summarized, especially from the synchrotron radiation sources and instruments with which the authors have principally been involved, namely SRS, Daresbury and ESRF, Grenoble as well as CHESS, Cornell and Elettra, Trieste. Rapid protein preparation and crystallization remain as major hurdles.