Use in ligand binding studies

Once a protein structure has been solved, the study of the association of small molecules with the protein may be accomplished relatively easily by means of difference Fourier syntheses. The method has been widely applied in the study of binding of inhibitors and pseudo-substrates to a large number of proteins and has provided the means by which active and allosteric sites may be located. It is assumed that the small ligand does not change the unit cell or perturb the protein substantially, and that the protein phases are approximately equal to those for the protein and ligand. Small changes in conformation can be distinguished as in conventional difference syntheses. The coefficients used are 

Errors in difference syntheses are proportional to the root mean square difference of FpL —Fpl and hence are much less than those in the native electron density map 

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