Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2

The results of quantum mechanics/molecular mechanics calculations of electron density changes upon oligopeptide hydrolysis by the matrix metalloproteinase-2 are utilized to discriminate between reactive and non-reactive enzyme–substrate complexes. Electron density depletion regions on the carbonyl carbon atom attacked by a catalytic water molecule are found on the 2D maps of electron density Laplacian in the reactive complexes. Also, the computed Fukui function quantitatively describes reactivity of the nucleophilic and electrophilic sites.