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Submission Date

Fall 2021


Matrix metalloproteinase 12 (MMP 12) is one of the twenty-three members of the peptidase M10 family which are primarily responsible for the breakdown of the extracellular matrix. MMP12 plays a key factor in the degradation of elastin and is commonly studied in the lungs of smokers, where MMP12 digests the elastin and serves as a chemokine to recruit a pro-inflammatory immune response. Thus, MMP12 is a major therapeutic target in wound healing and scar formation following a myocardial infarction. Students from the Honors Protein Modeling class at Nova Southeastern University modeled the interactions between MMP12 and various inhibitors. Using the protein data bank, an MMP12 protein complexed with the inhibitor called EEG under the code 3LIK was discovered. The structure was imported into JMOL: a protein visualization software. EEG intercalates into the S1 loop of the MMP12 protein without causing any disturbance to the loop's conformation. Murine trials were found with corresponding data for another MMP12 inhibitor known as AS111793 which was shown to reduce inflammation associated with cigarette smoke. A series of inhibitors were created using key components of EEG and AS111793. The binding was modeled on Py-Rx: a screening software used to dock the inhibitors. It was found that the hybrid compound created had a higher binding affinity than AS111793, but less affinity than EEG. This may be because a majority of the solvents and elements were removed from the inhibitor which did not allow the docking to occur.

How can we design an inhibitor with an enhanced binding affinity that is selective for MMP12 ?