Molecular mechanics and molecular orbital simulations on specific interactions between peroxisome proliferator-activated receptor PPARalpha and plasticizer.

Peroxisome proliferator-activated receptor alpha (PPARalpha) has various physiological functions such as lipid and glucose metabolism, inflammation and fibrosis in living organisms. Many types of ligand molecules such as phthalate and adipate esters control these physiological functions. In the present study, to elucidate the dependence of PPARalpha properties on ligand binding, we investigated stable structures and electronic properties for the complexes of PPARalpha and phthalate as well as adipate esters, which are used as a plasticizer, by molecular simulations based on molecular mechanics and molecular orbital methods. Furthermore, to elucidate the influence of these esters in vivo, we injected them into male mice and observed the change in the expression of PPARalpha-related enzymes. The comparison between the calculated and observed results indicates that the change in the expression has a correlation with the size of energy gaps between highest occupied and lowest unoccupied molecular orbitals of the complexes with mouse PPARalpha and esters.