Advances in multiple wavelength anomalous diffraction crystallography

In only a few years, multiple wavelength anomalous diffraction (MAD) phasing has advanced from an esoteric technique used in only a few favorable cases to the method of choice for solving new macromolecular structures. Before 1994, MAD phasing had been used for fewer than a dozen new structure determinations. In 1999 alone, well over 100 new structures were determined by MAD phasing. The meteoric rise in MAD applications resulted from the availability of new synchrotron beamlines, equipped with low bandpass optics, fast readout detectors, cryogenic cooling and user-friendly interfaces. The power of MAD phasing has been amplified by the availability of new computer programs for locating the positions of the anomalous scattering atoms and for calculating phases from the experimental data. Phasing by anomalous scattering techniques has been applied to structures as large as 640 kDa and 120 selenium atoms in the asymmetric unit. The practical size limitation for application of MAD phasing techniques has not yet been encountered.