The impact of ionization States of matrix metalloproteinase inhibitors on docking-based inhibitor design.

The influence of ionization states of hydroxamates and retrohydroxamates and the presence of zinc ions in the active site were investigated using the wild-type and E402Q mutant of MMP-9. The deprotonated hydroxamates showed a significantly enhanced enrichment factor in the presence of zinc ions. A pharmacophore model was developed based on the deprotonated compounds and was used to identify four structurally diverse compounds with antiproliferative activities.