The classical method of MAD phasing is similar to that described in Sec. except that there is no native structure factor and there is additional information present due to the anomalous scattering. The change in heavy atom scattering factor due to a change in X-ray energy is exactly analogous to, but in general smaller than, the isomorphous change affected by the addition of a heavy atom into the structure in the isomorphous replacement method and may be treated as such. The scattering factor however acts orthogonally to and is treated slightly differently. The method is an extension of Single Isomorphous Replacement with Anomalous Scattering (SIRAS)  .
The lack of native protein structure factor is accommodated by choosing a structure factor at one of the X-ray energies as a reference. The reference structure factor is defined in Fig. and its magnitude is given by an expression analogous to Eq. , i.e.
The phase of the reference structure factor is given by Eq. and in terms of the present variable system for structure factors measured at two energies and this may be written
A second expression for may be obtained by rearranging Eq. to give
Again Eqs. and together produce an unambiguous solution for the phase of .