To Probe Full and Partial Activation of Human Peroxisome Proliferator-Activated Receptors by Pan-Agonist Chiglitazar Using Molecular Dynamics Simulations.

ABSTRACT: Chiglitazar is a promising new-generation insulin sensitizer with low reverse effects for the treatment of type II diabetes mellitus (T2DM) and has shown activity as a nonselective pan-agonist to the human peroxisome proliferator-activated receptors (PPARs) (i.e., full activation of PPARγ and a partial activation of PPARα and PPARβ/δ). Yet, it has no high-resolution complex structure with PPARs and its detailed interactions and activation mechanism remain unclear. In this study, we docked chiglitazar into three experimentally resolved crystal structures of hPPAR subtypes, PPARα, PPARβ/δ, and PPARγ, followed by 3 μs molecular dynamics simulations for each system. Our MM-GBSA binding energy calculation revealed that chiglitazar m

SUBMITTER: Sullivan HJ 

PROVIDER: S-EPMC7152983 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature