Johnson & Johnson

---

Johnson & Johnson calculates binding affinities for Stromelysin-1 (MMP-3) inhibitors using method from Fujitsu

Stromelysin-1 is a matrix metalloproteinase (MMP-3). MMPs are zinc containing proteins associated with a variety of inflammatory, malignant and degenerative diseases and are thus attractive targets for drug development. Modeling of interactions between potential inhibitors of MMP-3 is hindered, however, by the fact that a proton shift and charge transfer occurs within the active site of the protein, ultimately resulting in a covalent Meta-Ligand (M-L) bond. Standard docking simulations model this binding interaction poorly.

Researchers at Johnson & Johnson* utilized BioMedCAChe to model the binding affinity of potential MMP-3 inhibitors using MOZYME, the proprietary linear scaling MO procedure, and COSMO solvation energies. They were able to model directly the metal center in the active site and the covalent M-L bond and thus account for the charge transfer and proton transfer which occurs during binding. In addition, the technique was found be useful for modeling the interactions of diverse ligands within the MMP-3 active site. This technique holds promise for dealing with binding interactions across a variety of classes of organometallic enzymes.

---