The majority of macromolecular structures solutions over the last thirty years have been by the isomorphous replacement method typically using complex ions of the heavy atoms Pt, Au, Hg, Pb and U (see Blundell & Johnson, Chap. 8 ). By far the most successful of these heavy atoms has been mercury because of its high affinity for binding to sulphur groups, for example through mercuration of cysteinyl groups not involved in disulphide bridges, to give isomorphous derivatives with only a very small number of highly occupied heavy atom sites making solution of the heavy atom partial structure by the difference Patterson method, possible if not straightforward. Single wavelength anomalous scattering experiments have played an additional role in the isomorphous replacement method by providing extra phase information through the violation of Friedel's law and in some cases has done away with the need for a second isomorphous derivative.
Multiple wavelength Anomalous Diffraction methods up until now have mainly been used for the solution of metallo-enzymes (see for example ,  and ), and seleno-methionyl proteins (see ,  and ). Metallo-enzymes typically contain heavy atoms from the 1st transition series of the periodic table and their neighbours. The K-edges of most of these metals fall within the X-ray energy range accessible by synchrotron radiation but are at low energies . In most of the cases studied K-edges have displayed only small deviations from theory  in the values near the absorption edge. This fact means that little advantage is to be gained by performing an optimised anomalous scattering measurement at the absorption maximum of the heavy metal concerned. In the case of proteins which have been engineered to contain a number of selenium atoms the K-edge lies at a usefully high energy () where radiation damage becomes less severe due to the reduced effect of absorption. In the best case the white line at the K absorption edge of Se can increase the value from to however this has been shown to be highly sensitive to the orientation of the selenium ligands with respect to the X-ray polarisation vector  resulting in shifts in the height and position of the absorption maximum.
A third style of experiment has also been carried out where calcium atoms present in some proteins have been substituted by heavier atoms from the lanthanide series. Two such cases involved substituting Ho  and Tb  atoms where observed white line maxima of and respectively were reported. In fact the metals in the lanthanide series in general are particularly good candidates for white line experiments   at the and edges at X-ray energies ranging from . In each of these cases experiments were performed at energies corresponding to the maximum, minimum and at a third energy chosen so as to obtain contrast in the value of .