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

作     者：BIDYUT MALLICK ASHISH RANJAN SHARMA MANOJIT BHATTACHARYA SANG-SOO LEE CHIRANJIB CHAKRABORTY 

作者机构：Department of Applied ScienceGalgotias College of Engineering and TechnologyKnowledge Park-IIGreater Noida201306India Institute for Skeletal Aging&Orthopedic SurgeryHallym University-Chuncheon Sacred Heart HospitalChuncheon-si24252Korea Department of ZoologyFakir Mohan UniversityVyasa ViharBalasore756020India Department of BiotechnologySchool of Life Science and BiotechnologyAdamas UniversityKolkata700126India 

出 版 物：《BIOCELL》 (生物细胞（英文）)

年 卷 期：2021年第45卷第4期

页      面：953-961页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 07[理学] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：supported by Hallym University Research Fund and by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2020R1C1C1008694&NRF-2020R1I1A3074575). 

主　　题：PPARγ Partial agonist Molecular simulation T2D Drug discovery 

摘      要：PPARγis 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 PPARγto determine the ligand specificity.It also helps to understand the ligand-binding domain(LBD)activity of PPARγduring the binding of the ligand.Further,a molecular dynamics simulation study was performed to determine the ligand biding stability in the PPARγLBD.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 theβ-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 theβ-sheet region.It shows the binding conformation of partial agonist(PPARγ)in the Pocket-II of PPARγLBD,which has a significant role in stabilizing theβ-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.