Molecular dynamics simulations reveal the role of ceramicine B as novel PPAR{\gamma} partial agonist against type 2 diabetes

Abstract

Peroxisome proliferator-activated receptors gamma (PPAR{\gamma}) are ligand-activated controllers of various metabolic actions and insulin sensitivity. PPAR{\gamma} is thus considered as an important target to treat type 2 diabetes. Available PPAR{\gamma} 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 PPAR{\gamma} ligand from a natural product. Our study suggests that the inhibition of ceramicine B in the PPAR{\gamma} 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 PPAR{\gamma} while avoiding the side effects associated with full agonists.