| Project/Area Number |
16K05657
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical chemistry
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| Research Institution | Okayama University |
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Principal Investigator |
Tomonari Sumi 岡山大学, 異分野基礎科学研究所, 准教授 (40345955)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | タンパク質 / 熱力学安定性 / 疎水性相互作用仮説 / 溶媒和自由エネルギー / シニョリン / 液体論 / 密度汎関数理論 / F1-ATPase / 化学-力学共役機構 / エネルギー変換効率 / SAXS / Model-potential-free解析 / 自由エネルギープロファイル / GCN4-p1 / 疎水性相互作用 / 圧力変性 / 高温変性 / 生物物理 / 蛋白質 |
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| Outline of Final Research Achievements |
Understanding the dominant factor in thermodynamic stability of proteins remains an open challenge. Kauzmann’s hydrophobic interaction hypothesis, which considers hydrophobic interactions between nonpolar groups as the dominant factor, has been widely accepted for about sixty years and attracted many scientists. The hypothesis, however, has not been verified or disproved because it is difficult, both theoretically and experimentally, to quantify the solvent effects on the free energy change in protein folding. Here, we developed a computational method for extracting the dominant factor behind thermodynamic stability of proteins and applied it to a small model chignolin. Decomposition of the free energy indicated that intramolecular interactions predominantly stabilized collapsed conformations, whereas solvent-induced interactions, including hydrophobic ones, destabilized them. These results obtained for chignolin were consistent with experimental observations for globular proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
タンパク質が示す多様な物性(変性，凝集，溶解，結晶化，液-液相分離)は，基礎科学として幅広い学術分野(化学，構造生物学，医学など)から強い関心を集めているだけでなく，バイオ医薬品の設計や品質管理等の応用にも関係する，社会的に重要な研究課題である．本研究により明らかにされた、タンパク質構造安定性の分子内直接相互作用メカニズムは，これまで長年信じられてきた仮説に関し，再検討する必要性を示唆しており，この根本的理解は今後のバイオ医薬品の設計指針の確立に置いて，極めて重要な位置を占める．
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