*2.1. Docking Studies*

A molecular operating environment (MOE) program was used in the current docking study. The validation of the docking accurately reproduced the binding conformation of the co-crystallized ligands with MMP proteins. The RMSD values were calculated between the co-crystallized poses and the docked poses of the same ligands in MMP-2 (PDB ID: 1HOV) and MMP-9 (PDB ID: 1GKC). Minor deviations of 1.30 and 0.75 A<sup>0</sup> , for MMP-2 and MMP-9, were observed, respectively (Figures 3 and 4). Such results indicated the validity of the docking studies.

**Figure 4.** Overlay of the co-crystallized pose (turquoise) and the re-docked pose (green) of **NFH** inside MMP-9 (PDB ID: 1GKC) during validation (RMSD = 0.75 A<sup>0</sup> ).
