39th Annual Student Research Conference
Allosteric inhibition of Matrix Metalloproteinase 9 (MMP-9) in silico as a potential cancer therapeutic
Dagmawit Kebede
Dr. Andrew Kauffmann and Dr. Bill R. Miller (A.T. Still University), Faculty Mentors
Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that promotes tumor invasion, metastasis, and angiogenesis through extracellular matrix degradation, making it an important therapeutic target in cancer. Traditional inhibitors target the catalytic Zn²? site, but this region is highly conserved among metalloproteinases, often leading to poor selectivity and side effects. Allosteric inhibition provides an alternative strategy by targeting distal binding pockets to modulate enzyme activity without directly interacting with the catalytic zinc site. In this study, the FTMap server was used to identify potential allosteric hotspots on MMP-9. Ligands were generated and docked using DOCK6. From these, 157 top-scoring complexes were selected for 250 ns molecular dynamics simulations in AMBER, and binding stability was evaluated using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) free energy calculations. Several ligands showed stable interactions within the predicted allosteric pocket, supporting the feasibility of selectively targeting allosteric sites in MMP-9 for inhibitor development.
Keywords: Matrix metalloproteinase-9, Allosteric inhibition, Molecular dynamics simulation, Zinc-dependent endopeptidase
Topic(s):Chemistry
Biochemistry and Molecular Biology
Biology
Presentation Type: Oral Presentation
Session: -2
Location: MG 1098
Time: 8:45