Identification of selective MMP-9 inhibitors through multiple e-pharmacophore, ligand-based pharmacophore, molecular docking, and density functional theory approaches

Journal of Biomolecular Structure & Dynamics
Srabanti Jana, Sushil K Singh

Abstract

Matrix metalloproteinase-9 (MMP-9) is a significant target for the development of drugs for the treatment of arthritis, CNS disorders, and cancer metastasis. The structure-based and ligand-based methods were used for the virtual screening (VS) of database compounds to obtain potent and selective MMP-9 inhibitors. Experimentally known MMP-9 inhibitors were used to grow up ligand-based three pharmacophore models utilizing Schrodinger suite. The X-ray crystallographic structures of MMP-9 with different inhibitors were used to develop five energy-optimized structure-based (e-pharmacophore) models. All developed pharmacophores were validated and applied to screen the Zinc database. Pharmacophore matched compounds were subjected to molecular docking to retrieve hits with novel scaffolds. The molecules with diverse structures, high docking scores and low binding energies for various crystal structures of MMP-9, were selected as final hits. The Induced fit docking (IFD) analysis provided significant information about the driving of inhibitor to approve a suitable bioactive conformational position in the active site of protein. Since charge transfer reaction occurs during receptor-ligand interaction, therefore, electronic features of hi...Continue Reading

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Citations

Feb 13, 2019·Journal of Biomolecular Structure & Dynamics·Cai YaoXianrong Qi
Mar 17, 2020·Journal of Biomolecular Structure & Dynamics·Sehrish JamalSyed Tarique Moin
Sep 3, 2020·Journal of Biomolecular Structure & Dynamics·Velu Shunmuga PriyaMani Vasanthi
Aug 31, 2021·Journal of Biomolecular Structure & Dynamics·Muthu Kumar Thirunavukkarasu, Ramanathan Karuppasamy
Oct 16, 2021·Journal of Chemical Information and Modeling·Binbin ChenQi Wang

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Methods Mentioned

BETA
X-ray

Software Mentioned

AutoDockTools
Glide SP
Epik
Prime
HTVS
MM
Glide
Ligprep
QPlog
Phase

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