Can Experimental Electron-Density Studies be Used as a Tool to Predict Biologically Relevant Properties of Low-Molecular Weight Enzyme Ligands?

The case of protease inhibitor model compounds incorporating an aziridine or epoxide ring is used to exemplify how application of experimental electron-density techniques can be used to explain the biological properties of low-molecular weight enzyme ligands. This is furthermore seen in the light of a comparison of crystal and enzyme environments employing QM/MM computations to elucidate to which extent the properties in the crystal can be used to predict behavior in the biological surrounding.