Ligand binding in protein crystal structures

When a substrate or inhibitor binds to a protein, it displaces water. As a result, electron density for ordered water is replaced by electron density for part of the ligand molecule. This means that there may be no appreciable peak in the difference map. In addition, because of somewhat incorrect phases, the substrate or inhibitor will appear in a difference map with reduced electron density, usually about half that of a well-phased map (half-weight AF map). Consequently, the practice has sometimes been to multiply coefficients. Often a map that combines the features of a difference map Fph Fp, enhanced by a factor of two, and of the native protein map Fp, is used. The coefficients of the Fourier synthesis are then  

FIGURE 9.15. A substrate binding to a protein shown by difference maps. The fit to the electron density map is better in (a) than in (b). 

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