MAD phasing: treatment of dispersive differences as isomorphous replacement information

A framework analogous to that used for the analysis of data in the method of isomorphous replacement is applied to the analysis of multi-wavelength anomalous-diffraction (MAD) data. The present method is advantageous in that refinement of parameters describing the anomalously scattering atoms in the structure can be carried out using nearly all the data, and in that phase information can be readily combined. The procedure described here involves an approximation in which it is assumed that the magnitude of the structure factor corresponding to anomalously scattering atoms in the unit cell is small compared to that corresponding to all other atoms in the structure. A model calculation is applied to a protein crystal with 682 non-H atoms in the asymmetric unit and two Se atoms as the anomalous scatterers. It is shown using this model calculation that the approximation used in this analysis does not substantially affect the accuracy of phase calculations for this MAD data. The method is demonstrated by application to MAD data collected on gene V protein.