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

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• 作者：Tomohiko Nakagawa ; Noriyuki Kurita ; Shinsaku Kozakai ; Shingo Iwabuchi ; Yoko Yamaguchi ; Masato Hayakawa ; Yuki Ito ; Toshifumi Aoyama ; Tamie Nakajima
• 关键词：Peroxisome proliferator-activated receptor ; Phthalate esters ; Molecular simulations ; Molecular mechanics method ; Molecular orbital method ; Electronic properties ; Ligand binding affinity
• 刊名：Journal of Molecular Graphics and Modelling
• 出版年：2008
• 出版时间：August 2008
• 年：2008
• 卷：27
• 期：1
• 页码：45-58
• 全文大小：2628 K

文摘

Peroxisome proliferator-activated receptor α (PPARα) 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 PPARα properties on ligand binding, we investigated stable structures and electronic properties for the complexes of PPARα 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 PPARα-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 PPARα and esters.