A simple interpretation of integrated direct methods - isomorphous replacement probability distributions

Integrated direct methods- isomorphous probability distributions [Hauptman (1982). Acta Cryst. A38, 289-294] are interpreted in terms of the familiar parameters of the isomorphous replacement method, the diffraction ratio and the differences in the diffraction intensities of a native protein and its heavy-atom derivative. The analysis shows that the reliability of the phase estimates is a function of the degree of heavy-atom substitution in the derivative. It clearly pinpoints the most favorable conditions for retrieving phase information from the intensity data of an isomorphous pair of structures. Finally, it provides a means to determine a priori the overall reliability of the phase estimates and to design the calculations accordingly.