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Published:
Mar 17, 2019Keywords:
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Main Article Content
Structural analysis and insight into novel MMP-13 inhibitors from natural chemiome as disease-modifying osteoarthritis drugs
Abstract
Methods: Computer-aided drug design (CADD) with virtual screening, ADME/Tox, molecular docking, molecular dynamics simulation, and MM-PBSA calculations were used in search of novel natural compounds that inhibit MMPs.
Results: From more than fifty thousand compounds, a single lead compound (IBS ID: 77312) was shortlisted using bias based on binding energy and drug-likeness. This lead compound synergistically bound to the S1 domain of MMP-13 protein through five hydrogen bonds. The interactions became stable within 100-nanosecond molecular dynamics simulation run. The in vitro data for the lead compound showed that its minimal non-lethal dose increased collagen content but decreased aggrecan level in chondrocytes.
Conclusion: This study has identified a natural lead compound that may pave the way for a novel DMOAD of natural origin against OA.
Keywords: Osteoarthritis, MMP-13, Natural chemiome, Disease-modifying osteoarthritis drug, Molecular docking
