39th Annual Student Research Conference
Computational Design of Matrix Metalloproteinase-9 (MMP-9) Inhibitors as Potential Cancer Therapeutics
Makda Gebreegziabher*, Dagmawit Kebede, and Haleluya T. Merga
Dr. Andrew Kauffmann, Faculty Mentor
Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent protein involved in extracellular matrix (ECM) breakdown leading to biological processes such as tissue remodeling and wound healing. In cancer, MMP-9 promotes tumor invasion and metastasis through excessive ECM degradation. However, due to its high homology with other MMPs, especially MMP-2, inhibitors like BB-94 failed clinically because of poor selectivity and off-target effects. To identify improved candidates, 397 compounds were generated from de novo drug design and 97 compounds were obtained from the PubChem database. Computational approaches including molecular docking, molecular dynamics simulations and binding free energy calculations were used to evaluate these potential compounds. The current top inhibitor showed a more favorable binding to MMP-9 than the control inhibitor, BB-94. Our results suggest several candidates for selective MMP-9 inhibition that could potentially lead to advances in cancer treatment. Other works include using alternate methods to identify improved compounds and testing their selectivity.
Keywords: Cancer, Computational, Drug design, Targeted Therapy
Topic(s):Biochemistry and Molecular Biology
Chemistry
Presentation Type: Poster Presentation
Session: -24
Location: Activities Room
Time: 2:30