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

The evolution of the brilliance of synchrotron radiation sources has allowe d combined functionalities of beamline optics for simultaneous high intensi ty, 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 a s at high diffraction resolution from macromolecular structures and their c omplexes. Rapid de novo protein structure determination is now achieved. Th e selenomethionine substitution method offers a definite way to incorporate anomalous scattering atoms in a protein for MAD, although MAD is also a ve ry versatile approach applicable to metalloproteins and to cases of many he avy atoms found useful in isomorphous derivative preparation (especially ut ilization of non-isomorphous derivatives). Detector developments, especiall y image-plate scanners and now CCDs, have revolutionized diffraction data q uality and speed of data acquisition, with further developments, such as th e pixel detector, in store. Cryocooling of the sample has greatly alleviate d radiation damage problems. Computer hardware capabilities have also chang ed incredibly. Coordinated software developments for protein crystallograph y have been achieved [Collaborative Computational Project, Number 4 (1994). Acta Cryst. D50, 760-763]. Protein crystallography and synchrotron radiati on is capable of yielding 'genome level' numbers of protein structures. Res ults and capabilities are presented and summarized, especially from the syn chrotron radiation sources and instruments with which the authors have prin cipally been involved, namely SRS, Daresbury and ESRF Grenoble as well as C HESS, Cornell and Elettra, Trieste. Rapid protein preparation and crystalli zation remain as major hurdles.