Influence of genetic polymorphism on three-dimensional structure and structural flexibility of drug metabolizing enzyme

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460034
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Meijo University (2016); Kanazawa University (2014-2015)
• Principal Investigator: Oda Akifumi 名城大学, 薬学部, 教授 (50433511)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬物代謝酵素 / 遺伝多型 / 構造揺らぎ / 基質認識 / 分子動力学シミュレーション

Outline of Final Research Achievements

In this study, the influence of the genetic polymorphisms on the static three-dimensional structures and the structural flexibilities of the drug metabolizing enzymes were evaluated by using molecular simulations. The genetic polymorphisms cause the amino acid mutations in the gene product proteins, and the mutated residues cause the changes of the static and dynamic structural properties of the proteins. In the drug metabolizing enzymes, such as cytochrome P450s, the static structures of proteins changed not only around the mutated residues, but also in the distant portion of proteins because of the transformation of the hydrogen network. In addition, because the structural flexibility of proteins were changed by the mutation, the interaction between drug metabolizing enzymes and the other molecules such as water were reduced.

Free Research Field

計算化学