Informational thermodynamics of biomolecular crowding systems in water

2021 Fiscal Year Final Research Report

• Project Area: Chemical Approaches for Miscellaneous / Crowding Live Systems
• Project/Area Number: 17H06353
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Kobe University
• Principal Investigator: Tanaka Shigenori 神戸大学, システム情報学研究科, 教授 (10379480)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: 分子夾雑 / 分子動力学法 / 生体高分子 / 会合解離 / 自由エネルギー / アミロイド / 熱伝導 / 量子生命科学

Outline of Final Research Achievements

In response to the question of "how the intracellular molecular crowding environment affects the functional expression of biomolecules", we have developed computational methods to efficiently describe the processes of association and dissociation of protein multimers mainly based on the molecular dynamics (MD) simulation. We thus performed actual application calculations, and quantitatively elucidated their molecular mechanisms. Specifically, we targeted amyloid aggregates involved in neurological diseases and Ras protein complexes related to cancer. In addition to describing their association / dissociation dynamics thermodynamically from the viewpoint of free energy and thermal energy, the roles played by substrates such as ATP and GTP were also microscopically elucidated. Furthermore, we also tried to theoretically describe heat conduction, temperature relaxation, and quantum characteristics in biomolecular systems.

Free Research Field

計算生物学

Academic Significance and Societal Importance of the Research Achievements

従来の分子生物学・細胞生物学は分子レベルから生命機能を解き明かす上で重要な多くの知見を蓄積してきたが、細胞内の分子夾雑環境が果たす役割については未解明の部分が多かった。本研究では特に、タンパク質や核酸などの生体高分子が形成する複合体に注目し、その形成や崩壊などの過程が微視的にどのように起きるのかを可視化・定量化する計算機シミュレーション技術を開発した。また、それに基づき、アルツハイマー病やガンなどに関わる分子系の応用計算を行い、細胞内のATPやGTPなどの共存分子が演じる役割についても新たな知見を得た。加えて、温度生物学や情報熱力学、量子生命科学などの新たな学術領域への展開も試みた。