A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Density functional theory and molecular dynamics simulation support Ganoderma lucidum triterpenoids as broad range antagonist of matrix metalloproteinases
Tekijät: Shiv Bharadwaj, Kyung Eun Lee, Vivek Dhar Dwivedi, Umesh Yadava, Matthias Nees, Sang Gu Kang
Kustantaja: ELSEVIER
Julkaisuvuosi: 2020
Journal: Journal of Molecular Liquids
Tietokannassa oleva lehden nimi: JOURNAL OF MOLECULAR LIQUIDS
Lehden akronyymi: J MOL LIQ
Artikkelin numero: ARTN 113322
Vuosikerta: 311
Sivujen määrä: 10
ISSN: 0167-7322
DOI: https://doi.org/10.1016/j.molliq.2020.113322
Tiivistelmä
Matrix metalloproteinases (MMPs) actively caused enzymatic proteolysis of extracellular matrix (ECM) and cell surface proteins, suggested as critical for connective tissue that results in progressive aging and other diseases. Numerous efforts have been conducted to design the broadrange of synthetic inhibitors for MMPs, but none of them have successfully passed the clinical trials. Recently, Ganoderma lucidum triterpenoids were reported with significant medicinal beneficial effects, including free radical-scavengers and anti-cancer activity. However, their concealed property as an antagonist of MMPs is not yet explored. Hence, this study attempts to elucidate the Ganoderma lucidum triterpenoids potential as broad range of MMPs inhibitor using computational chemistry approaches. Herein, 100 Ganoderma lucidum triterpenoids were virtually screened against the model MMPs, i.e. gelatinase (MMP2), stromelysin (MMP3), collagenase (MMP8), and metalloelastase (MMP12) followed by ADME profiling, and results into the prediction of 14 bioactive triterpenoids as broad-spectrum MMPs inhibitors. Furthermore, stringent extra precision molecular docking by Glide protocol revealed Ganoderiol D and Ganodermanotriol as potential antagonists of model MMPs. These triterpenoids were further studied by density functional methods and in docked complexes ofMMPs using molecular dynamics simulation, predicted the non-reactivity of triterpenoids, and established the MMPs-triterpenoids complex stability by strong intermolecular interactions (hydrogen bonds, hydrophobic and polar interactions), respectively. Furthermore, binding free energy calculations deduced the significant involvement of coulomb and van der Waals forces in the respective MMP-triterpenoid complexes stability, supported the Ganoderiol D and Ganodermanotriol as broad range antagonist of MMPs. (C) 2020 Elsevier B.V. All rights reserved.
Matrix metalloproteinases (MMPs) actively caused enzymatic proteolysis of extracellular matrix (ECM) and cell surface proteins, suggested as critical for connective tissue that results in progressive aging and other diseases. Numerous efforts have been conducted to design the broadrange of synthetic inhibitors for MMPs, but none of them have successfully passed the clinical trials. Recently, Ganoderma lucidum triterpenoids were reported with significant medicinal beneficial effects, including free radical-scavengers and anti-cancer activity. However, their concealed property as an antagonist of MMPs is not yet explored. Hence, this study attempts to elucidate the Ganoderma lucidum triterpenoids potential as broad range of MMPs inhibitor using computational chemistry approaches. Herein, 100 Ganoderma lucidum triterpenoids were virtually screened against the model MMPs, i.e. gelatinase (MMP2), stromelysin (MMP3), collagenase (MMP8), and metalloelastase (MMP12) followed by ADME profiling, and results into the prediction of 14 bioactive triterpenoids as broad-spectrum MMPs inhibitors. Furthermore, stringent extra precision molecular docking by Glide protocol revealed Ganoderiol D and Ganodermanotriol as potential antagonists of model MMPs. These triterpenoids were further studied by density functional methods and in docked complexes ofMMPs using molecular dynamics simulation, predicted the non-reactivity of triterpenoids, and established the MMPs-triterpenoids complex stability by strong intermolecular interactions (hydrogen bonds, hydrophobic and polar interactions), respectively. Furthermore, binding free energy calculations deduced the significant involvement of coulomb and van der Waals forces in the respective MMP-triterpenoid complexes stability, supported the Ganoderiol D and Ganodermanotriol as broad range antagonist of MMPs. (C) 2020 Elsevier B.V. All rights reserved.
Turun yliopiston Tutkimustietojärjestelmän portaali