The MAD phasing method in macromolecular crystallography: general principles and the problem of the anisotropy of anomalous scattering

Abstract Several macromolecular structures have been solved with the Multiplewavelength Anomalous Diffraction (MAD) method in the recent years (Kahn et al. 1985, Korszun 1987, Krishna Murthy et al., 1988, Guss et al., 1988, Hendrickson et al. 1988, Hendrickson, Pahler et al. 1989, Graves et al., 1990). These successes have been made possible by the availability of tunable X-ray sources, the development of efficient area detectors and by advances in the methods for analysis of MAD data. Now the instrumentation is in place to make highly accurate measurements on macromolecular crystals so as to exploit the anomalous signal in direct phase determination. In this contribution we describe briefly the theoretical basis, experimental requirements and computational implementation of the MAD method (a more detailed review can be found in Fourme Hendrickson, 1990). In the last part we treat a problem specific to MAD, namely the effect of the anisotropy of anomalous scattering on the phase determination.