Open Access

ARTICLE

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

by Bidyut Mallick^1,#, Ashish Ranjan Sharma^2,#, Manojit Bhattacharya³, Sang-Soo Lee^1,*, Chiranjib Chakraborty^4,*

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, ; Chiranjib Chakraborty,
# These authors contributed equally to this work

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

Received 25 December 2020; Accepted 03 February 2021; Issue published 22 April 2021

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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