Institute of Multidisciplinary Research for Advanced Materials, Tohoku University


LAST UPDATE 2023/08/07

  • 研究者氏名
    Researcher Name

    田口真彦 Masahiko TAGUCHI
    助教 Assistant Professor
  • 所属
    Professional Affiliation

    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University

    有機・生命科学研究部門 量子ビーム構造生物化学研究分野
    Division of Organic- and Bio-materials Research, Quantum Beam-based Structural Biology and Chemistry
  • 研究キーワード
    Research Keywords

    Chemical reaction in biomolecular system
    Molecular simulation
    Hybrid QM/MM method
Research Subject
Understanding of biomolecular function by computational science linked with time-resolved experiment and its application

研究の背景 Background

タンパク質分子の構造を原子レベルで時分割測定できる技術が開発され, その機能発現過程を直接視ることが可能となってきています. 一方で計算科学分野においても, タンパク質分子に特有な化学反応と遅い構造変化の両立した記述を可能にする方法論が開発されてきています. これらの技術を連携することにより, タンパク質分子の機能発現に伴う動的過程の理解が格段に進展することが期待されます.

Time-resolved measurement technique for structure of protein molecule at atomic level enables us to directly visualize functional expression process of protein molecule. On the other hands, in computational science field, a method compatibly describing chemical reaction and slow conformational change which are characteristic for protein molecule is now available. Linking the computational method with the time-resolved data expects us to deepen understanding for dynamical process of protein molecule upon its functional expression.

研究の目標 Outcome

時分割実験と連携し, タンパク質分子の機能発現に伴う動的過程を分子シミュレーションにより明らかにします. 反応プロファイルを補完するために, プロトン化状態等の化学構造の同定や遷移状態モデリングを行います. また, 機能発現に至るまでの化学反応に端を発する連鎖的な構造変化を捉えます. これらの研究を通して, タンパク質分子における構造と機能の関係性に対する理解を深め, “機能の多様性と進化による機能転換”に関する知見の獲得を目指します.

We clarify dynamical process of protein molecule upon its functional expression using molecular simulation linked with time-resolved measurement. To complement the chemical reaction profile, we identify the chemical structure such as protonation state and model the transition state. Also, we capture the consecutive conformational change from local chemical reaction to functional expression. Through the research, we will deepen the understanding of relationship between structure and function of protein molecule and try to find a concept of “functional diversity and functional conversion by evolution”.

研究図Research Figure

Fig.1. HIV-1 protease with inhibitor. a QM/MM simulation system. b Representative snapshots of QM/MM simulation samples and MM ones.

Fig.2. LOV photoreceptor protein. a Photoactive region at initial and QM/MM convergence point. b Protein structure of dark state (purple) and light state (green).

Fig.3. BLUF photoreceptor protein. a Schematic figure to explain spin-allowed one electron transition upon light absorption and examples of molecular orbital. b Snapshots of molecular simulation for dark and light state (left and right).

文献 / Publications

J. Chem. Inf. Model. 62, 1328 (2022). Curr. Opin. Struc. Biol. 71, 7 (2021). Phys. Rev. B 97, 104514 (2018). J. Phys. Soc. Japan 85, 084704 (2016). Phys. Rev. B 92, 024507 (2015).