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PPARγ LBD and its ligand specificity reveal a selection of potential partial agonist: Molecular dynamics based T2D drug discovery initiative

BIDYUT MALLICK1,#, ASHISH RANJAN SHARMA2,#, MANOJIT BHATTACHARYA3, SANG-SOO LEE1,*, CHIRANJIB CHAKRABORTY4,*

1 Department of Applied Science, Galgotias College of Engineering and Technology, Knowledge Park-II, Greater Noida, 201306, India
2 Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, 24252, Korea
3 Department of Zoology, Fakir Mohan University, Vyasa Vihar, Balasore, 756020, India
4 Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, 700126, India

* Corresponding Authors:Sang-Soo Lee, email; Chiranjib Chakraborty, email
# These authors contributed equally to this work

BIOCELL 2021, 45(4), 953-961. https://doi.org/10.32604/biocell.2021.015530

Abstract

PPARγ is a peroxisome proliferator-activated receptor (PPAR) family protein and is a target for type 2 diabetes (T2D). In this paper, we have performed a molecular docking analysis between ligand molecules (CID9816265, CID11608015, CID20251380, CID20251343, CID20556263, CID624491, CID42609928, and CID86287562) and PPARγ to determine the ligand specificity. It also helps to understand the ligand-binding domain (LBD) activity of PPARγ during the binding of the ligand. Further, a molecular dynamics simulation study was performed to determine the ligand biding stability in the PPARγ LBD. Its ligand specificity informed us about the potentiality of selecting a partial agonist. The study also shows the binding conformation of Ceramicine B having hydrogen bonding affinity with a tricyclic polar head and stabilized the β-sheet region. On the other hand, the tricyclic polar head of nimbolide also formed hydrogen bonding (Ser342), but it shows a lesser degree of stabilization in the β-sheet region. It shows the binding conformation of partial agonist (PPARγ) in the Pocket-II of PPARγ LBD, which has a significant role in stabilizing the β-sheet region. It might help to regulate ERK/Cdk5 mediated phosphorylation of Ser245. The study helps us understand the valid pose of a set of ligands confirmation and target protein conformation using docking and molecular dynamics study. This in silico study will also help to initiate a drug discovery process of T2D.

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APA Style
MALLICK, B., SHARMA, A.R., BHATTACHARYA, M., LEE, S., CHAKRABORTY, C. (2021). PPARγ LBD and its ligand specificity reveal a selection of potential partial agonist: molecular dynamics based T2D drug discovery initiative. BIOCELL, 45(4), 953-961. https://doi.org/10.32604/biocell.2021.015530
Vancouver Style
MALLICK B, SHARMA AR, BHATTACHARYA M, LEE S, CHAKRABORTY C. PPARγ LBD and its ligand specificity reveal a selection of potential partial agonist: molecular dynamics based T2D drug discovery initiative. BIOCELL . 2021;45(4):953-961 https://doi.org/10.32604/biocell.2021.015530
IEEE Style
B. MALLICK, A.R. SHARMA, M. BHATTACHARYA, S. LEE, and C. CHAKRABORTY "PPARγ LBD and its ligand specificity reveal a selection of potential partial agonist: Molecular dynamics based T2D drug discovery initiative," BIOCELL , vol. 45, no. 4, pp. 953-961. 2021. https://doi.org/10.32604/biocell.2021.015530



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