Thermodynamic analysis of bimolecular assembly driven by solvent water

• Project/Area Number: 15K05254
• 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: Himeji Dokkyo University
• Principal Investigator: Harano Yuichi 姫路獨協大学, 薬学部, 准教授 (60456259)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 生体分子 / 熱力学 / 溶液化学 / 生物物理学 / 理論創薬 / 溶媒和熱力学 / 結合自由エネルギー / in silico創薬 / in silico 創薬 / 構造活性相関 / 蛋白質 / 水和自由エネルギー

Outline of Final Research Achievements

Because the processes of biomolecular autonomy happen in a liquid phase, existence of "the water" greatly participates. In addition, the important biomolecular behavior observed as an experiment is a time scale of more than sec (depending on a system day - month). It is necessary for us to understand that integrated the molecular aspects and thermodynamics for all systems, containing the water with a biological molecule.　In this study, we clarify how a thermodynamic property of the water participates by describing the free energy landscape for the structural change of the huge biological molecule using a high speed numeration of the hydration free energy that the study group of us developed based on theoretical chemistry.

Academic Significance and Societal Importance of the Research Achievements

本研究は生体分子の自律化メカニズムを、生体分子そのものに求めるのではなく、水溶媒環境を含めた全系として捉える点に特色があるため、液体理論のバイオ研究への応用という点での特色があるとともに「分子の集合・離散」という点では「タンパク質-リガンド結合」のエネルギー論として創薬の基礎を築くものである。
また、本研究で用いる理論的手法は、全原子モデルで記述されているので、一般的な理論化学的手法である分子シミュレーション技術や量子化学的手法と融合させることにより、より広範囲なエネルギー論が可能になる。本研究は理論研究にとどまらず、実験とのダイレクトな共同研究が可能になった。

Research Products

• [Journal Article] Glycosaminoglycan Binding and Non-endocytic Membrane Translocation of Cell-permeable Octaarginine Monitored by Real Time In-cell NMR Spectroscopy (2017)
  • Author(s): Y. Takechi-Haraya, K. Aki, Y. Tohyama, Y. Harano, T. Kawakami, H. Saito, E. Okamura
  • Journal Title: Pharmaceuticals Volume: 10 Issue: 2 Pages: 42-60
  • DOI: 10.3390/ph10020042
  • Peer Reviewed / Open Access
• [Journal Article] Water based on a molecular model behaves like a hard-sphere solvent for a nonpolar solute when the reference interaction site model and related theories are employed (2016)
  • Author(s): T. Hayashi, H. Oshima, Y. Harano, M. Kinoshita
  • Journal Title: J. Phys.: Condens. Matter Volume: 28 Issue: 34 Pages: 344003-344003
  • DOI: 10.1088/0953-8984/28/34/344003
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] An Accurate and Efficient Computation Method of the Hydration Free Energy of a Large, Complex Molecule (2015)
  • Author(s): T. Yoshidome, T. Ekimoto, N. Matubayasi, Y. Harano, M. Kinoshita, M. Ikeguchi
  • Journal Title: J. Chem. Phys. Volume: 142 Pages: 175101-175101
  • Peer Reviewed