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

Abstract

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

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