Statistical mechanics study on higher-order structure formation of proteins driven by water and ions

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K05519
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological physics/Chemical physics/Soft matter physics
• Research Institution: Kyushu University
• Principal Investigator: Yoshida Norio 九州大学, 理学研究院, 准教授 (10390650)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 理論化学 / 統計力学 / 液体の積分方程式理論 / ドメインスワッピング

Outline of Final Research Achievements

We targeted domain swapping of Uma cytochrome c (cyt c) and sought to elucidate the role of solvents in this process. The contribution of structural energy, structural entropy, and hydration free energy of each amino acid residue to dimer stabilization was analyzed, and it was found that the electrostatic repulsion of dissociative residues between the two cyt c's played a major role. Furthermore, the structural changes around heme, which are responsible for the inactivation of cyt c by dimer formation, are revealed at the atomic level. The effects of anions on dimer formation were then examined, and the differences in protein-ion interactions between different ion species were clarified.

Free Research Field

理論化学

Academic Significance and Societal Importance of the Research Achievements

本研究計画では，3D-RISM理論を基幹として理論構築を行うことに一つの特色がある。本研究で用いた手法を用いることで、これまで困難であったイオンを含む溶液が駆動する生体分子の大域的構造変化・高次構造形成に対し、知見を得ることができる。この手法により、ドメインスワッピングのみならず生体分子の高次構造形成の分子論的解析が可能となり、生体高分子の高次構造デザインによる、生体分子機能性材料設計、オリゴマー形成疾患治療法開発などへの展開が期待できる。