Molecular dynamics simulations reveal the role of ceramicine B as novel PPARγ partial agonist against type 2 diabetes

2018/08/25 by Bidyut Mallick, Mallick, Bidyut
Biochemistry, Genetics and Molecular Biology · #Biomolecules (q-bio.BM) #Eicosanoids and Hypertension Pharmacology #FOS: Biological sciences #Metabolism, Diabetes, and Cancer #Peroxisome Proliferator-Activated Receptors #q-bio.BM

paper · pdf · doi:10.48550/arxiv.1808.08375

arxiv created 2018/08/25 · openalex publication_date 2018/08/25 · arxiv updated 2018/08/28 · openalex created_date 2022/08/03 · openalex updated_date 2026/07/28

Abstract

Peroxisome proliferator-activated receptors gamma (PPARγ) are ligand-activated controllers of various metabolic actions and insulin sensitivity. PPARγ is thus considered as an important target to treat type 2 diabetes. Available PPARγ drugs (full agonists) have robust insulin-sensitizing properties but are accompanied by severe side effects leading to complicated health problems. Here, we have used molecular docking and a molecular dynamics simulation study to find a novel PPARγ ligand from a natural product. Our study suggests that the inhibition of ceramicine B in the PPARγ ligand-binding domain (LBD) could act as a partial agonist and block cdk5-mediated phosphorylation. This result may provide an opportunity for the development of new anti-diabetic drugs by targeting PPARγ while avoiding the side effects associated with full agonists.

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