Screening of Placental Proteins Against Proteases for their Potential Use in Osteoarthritis: A Computational Approach
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Published:15 Dec 2023
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Special Collection: 2023 ebook collection
J. J. James, P. Pavadai, and K. V. Sandhya, in Current Trends in Drug Discovery, Development and Delivery (CTD4-2022), ed. M. Murahari, B. N. Nalluri, and G. Chakravarthi, Royal Society of Chemistry, 2023, vol. 358, pp. 57-69.
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Osteoarthritis is a chronic joint condition owing to increasing articular cartilage weakening and deterioration. Novel agents targeting articular cartilage molecular mechanisms seem to be most promising. The placental tissues are biocompatible, immunoprivileged and rich in bio factors such as growth factors, cytokines, extracellular matrix and proteins. Placental proteins might reduce cartilage degradation through suppressing the expression of matrix metalloproteases. This study focuses on screening placental proteins against proteases using protein-protein docking and dynamic studies. Protein-protein docking was performed on twenty-six ligand proteins present in placental tissue against matrix metalloproteinase 13 by ZDOCK server and visualized through Biovia Discovery studio. Molecular dynamic study was carried out by DESMOND. Most of the placental proteins were found to have better binding to matrix metalloproteinase 13. Protein-protein docking study showed scores ranging from 1046.272 to 2229.332. Among all the proteins, metalloproteinase inhibitor 3 and plasminogen activator inhibitor 1 scores were found to be 2229.332 and 2131.215 respectively. These ligand proteins bound tightly with the target protein, indicated by greater number of hydrogen bond interactions on the surfaces. Molecular dynamic studies were carried out for the two complexes, complex was found to be stable during molecular dynamic simulation. From the results, metalloproteinase inhibitor 3 and plasminogen activator inhibitor 1 of placenta are found to be a promising candidate for the treatment of osteoarthritis. Based on these findings placental protein can be explored for its anti-arthritis property.