Identification of Novel Natural Product Inhibitors against Matrix Metalloproteinase 9 Using Quantum Mechanical Fragment Molecular Orbital-Based Virtual Screening Methods.

ABSTRACT: Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases involved in multiple cellular processes. Among the MMP isoforms, MMP-9 regulates cancer invasion, rheumatoid arthritis, and osteoarthritis by degrading extracellular matrix proteins present in the tumor microenvironment and cartilage and promoting angiogenesis. Here, we identified two potent natural product inhibitors of the non-catalytic hemopexin domain of MMP-9 using a novel quantum mechanical fragment molecular orbital (FMO)-based virtual screening workflow. The workflow integrates qualitative pharmacophore modeling, quantitative binding affinity prediction, and a raw material search of natural product inhibitors with the BMDMS-NP library. In binding affinity prediction, we made a scoring function wit

SUBMITTER: Lim H 

PROVIDER: S-EPMC9030947 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature