Modelling the interactions of MMP enzymes with catalytic zinc using DFT methods

Matrix Metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the remodeling of the extracellular matrix (ECM) and various pathological conditions. High MMP-9 activity is associated with the progression of numerous diseases, including cancer (breast, lung, pancreatic, ovarian, etc.), cardiovascular diseases, and arthritis. This thesis aims to investigate the inhibitory effects of Ficus Deltoidea (FD) leaf extract on MMP-9 and to explore the molecular mechanisms underlying these effects. Thus, it will examine whether the bioactive compounds present in FD leaf extract, vitexin and isovitexin, have an inhibitory effect on MMP-9. Using the DFT method, the lowest energy level structures were created, and HOMO-LUMO analysis, UV calculations, and NBO charges of these structures were calculated. The interactions of these compounds with MMP-9 were analyzed based on the obtained results. The results indicate that vitexin and isovitexin found in Ficus Deltoidea leaf extract can inhibit the MMP-9 enzyme and that these compounds could be used as potential biological agents in medical applications. DFT calculations reveal the molecular properties of these compounds and their interactions with MMP-9 in detail. It is observed that the stability of Zn-containing complexes increases, especially in polar solvents like water and methanol. This helps form more stable, lower-energy structures. In this thesis research, it is observed that complexes formed in water and methanol solvent environments create more stable structures and gain stability through hydrogen bonding. The obtained results demonstrate that vitexin and isovitexin inhibit the MMP-9 enzyme, with vitexin forming a more stable complex with MMP-9.