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蛋白質の大振幅ゆらぎの理論解析:構造変化経路から天然変性まで

Publicly Offered Research

Project AreaMolecular Science of Fluctuations toward Biological Functions
Project/Area Number 23107716
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionKyoto University

Principal Investigator

高田 彰二  京都大学, 理学(系)研究科(研究院), 教授 (60304086)

Project Period (FY) 2011-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords蛋白質 / シミュレーション / 大振幅ゆらぎ / 天然変性
Research Abstract

アロステリック蛋白質の大振幅ゆらぎ:大振幅ゆらぎを計算するためには長時間のシミュレーションが不可欠であり、そのためにはモデルの粗視化が有効である。我々はまず、全原子力場のエネルギーとゆらぎ情報をもとに粗視化モデルを構築することを試みた。AMBERエネルギー関数で計算したアミノ酸対の相互作用エネルギーに比例する相互作用をもち、ゆらぎの大きさがAMBERによるMDとよく一致するようなアミノ酸分解能の郷モデル(AICG2モデル)を構築した.
天然変性蛋白質の構造アンサンブル構築:天然変性蛋白質の構造アンサンブルをモデリングするために、変性領域を10数残基の断片に分割し、各々について全原子モデルのレプリカ交換MDを行い、そのとき得られる分布を利用してタンパク質全長の粗視化モデルを構築する手法を開発した。この手法を、癌抑制遺伝子産物p53の変性領域に適用し、得られたアンサンブルからNMRや溶液散乱プロファイルを計算し、それが実験とよく合うことを示した。
大きくゆらぐ蛋白質p53のDNA探索機構研究:p53は癌抑制性の多機能転写因子であり、細胞周期に関わる多数のタンパク質の転写を制御する。転写因子は一般に長いゲノムDNA上の特異的結合部位を効率よく探索する必要がある。転写因子が、いかにして速やかにターゲットを探索できるのか、という問題は重要な基礎問題である。我々は、上記で開発した手法を駆使してp53-DNA複合体の粗視化モデルを構築し、それを用いて、p53-DNA複合体の粗視化シミュレーションを行うことにより、生理的な塩濃度下で、C末端ドメインがDNA上をスライディングする一方で、コアドメインは探索中にDNAとの結合、解離を繰り返すことを明らかにした。このメカニズムは、近年の一分子実験の結果を説明するために提唱されたモデルと一致する。。

Current Status of Research Progress
Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (51 results)

All 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (40 results) (of which Invited: 2 results)

  • [Journal Article] RESPAC : Method to Determine Partial Charges in Coarse-greined Prote in Model and Its Application to DNA-Binding Proteins' Journal of Chemical Theory and Computation2014

    • Author(s)
      Tsuyoshi Terakawa and Shoji Takadae
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 10 Issue: 2 Pages: 711-721

    • DOI

      10.1021/ct4007162

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug Uptake Pathways of Multidrug Transporter AcrB Studied by Molecular Simulations and Site-Directed Mutagenesis Experiments2013

    • Author(s)
      Xin-Qiu Yao, Nobuhiro Kimura, Satoshi Murakami, and Shoji Takada
    • Journal Title

      Journal of the American Chemical Society

      Volume: 135 (20) Issue: 20 Pages: 7474-7485

    • DOI

      10.1021/ja310548h

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATP hydrolysis mechanism in kinesin studied by combined quantum-mechanical molecular-mechanical metadynamics2013

    • Author(s)
      M. J. McGrath、I-F. W. Kuo, S.Hayashi, S. Takada
    • Journal Title

      J. Amer. Chem. Soc.

      Volume: (in press) Issue: 24 Pages: 8908-891

    • DOI

      10.1021/ja401540g

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Energy landscape and multiroute folding of topologically complex proteins adenylate kinase and 2ouf-knot2012

    • Author(s)
      W. Li, T. Terakawa, W. Wang, S.Takada
    • Journal Title

      Proc. Nat. Acad. Sci. USA

      Volume: 44 Issue: 44 Pages: 17789-17794

    • DOI

      10.1073/pnas.1201807109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coarse-grained structure-based model for RNA - protein complexes developed by fluctuation matching2012

    • Author(s)
      Naoto Hori, Shoji Takada
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 8 Issue: 9 Pages: 3384-3394

    • DOI

      10.1021/ct300361j

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 searches on DNA by rotation-uncoupled sliding at C-terminal tails and restricted hopping of core domains2012

    • Author(s)
      T. Terakawa, H. Kenzaki, S. Takada
    • Journal Title

      J. Amer.Chem. Soc.

      Volume: 134 Issue: 35 Pages: 14555-14562

    • DOI

      10.1021/ja305369u

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rigor of cell fate decision by variable p53 pulses and roles of cooperative gene expression by p532012

    • Author(s)
      Y. Murakami and S. Takada
    • Journal Title

      BIOPHYSICS

      Volume: 8 Pages: 41-50

    • DOI

      10.2142/biophysics.8.41

    • NAID

      130002061596

    • ISSN
      1349-2942
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coarse-grained molecular simulations of large biomolecules2012

    • Author(s)
      S. Takada
    • Journal Title

      Curr. Opinion Struct. Biol.

      Volume: Vol.22 Issue: 2 Pages: 130-137

    • DOI

      10.1016/j.sbi.2012.01.010

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural comparison of F1-ATPase: Interplay among enzyme structures, catalysis,and rotations2011

    • Author(s)
      K. Okazaki S. Takada
    • Journal Title

      Structure

      Volume: vol.19 Issue: 4 Pages: 588-598

    • DOI

      10.1016/j.str.2011.01.013

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CafeMol : A coarse-grained biomolecular simulator for simulating proteins at work2011

    • Author(s)
      Hiroo Kenzaki, Nobuyasu Koga, Naoto Hori, Ryo Kanada, Wenfei Li, Kei-ichi Okazaki, Xin-Qiu Yao, Shoji Takada
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 7 Issue: 6 Pages: 1979-1989

    • DOI

      10.1021/ct2001045

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiscale ensemble modeling of intrinsically disordered proteins: p53 N-terminal domain2011

    • Author(s)
      T. Terakawa, S. Takada
    • Journal Title

      Biophys. J

      Volume: vol.101 Issue: 6 Pages: 1450-1458

    • DOI

      10.1016/j.bpj.2011.08.003

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 転写因子p53はDNA上をどのように走査するか?分子シミュレーションによる研究2012

    • Author(s)
      寺川剛, 高田彰二
    • Organizer
      第5回京阪奈セミナー
    • Place of Presentation
      関西光科学研究所(木津市)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 粗視化分子動力学計算によるリボソームにおける翻訳伸長機構の研究2012

    • Author(s)
      堀直人、高田彰二
    • Organizer
      第1回RIBOSOME MEETING
    • Place of Presentation
      広島大学生物生産学部(東広島市)
    • Year and Date
      2012-03-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-grained molecular simulations of large biomolecules : From theory to applications2012

    • Author(s)
      Shoji Takada
    • Organizer
      The 9th Fukui Inst Fundamental Chemistry Seminar
    • Place of Presentation
      Fukui Institute for Fundamental Chemistry (Kyoto)(招待講演)
    • Year and Date
      2012-03-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] 蛋白質のフォールディング、ミスフォールディングと会合:シミュレーションによるアプローチ2012

    • Author(s)
      高田彰二
    • Organizer
      神戸大学先端融合科学シンポジウム「タンパク質アセンブリ-会合、超分子化、凝集-」
    • Place of Presentation
      神戸大学(神戸市)(招待講演)
    • Year and Date
      2012-01-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-Grained simulations of proteins, nucleic acids, and their complexes2012

    • Author(s)
      Shoji Takada
    • Organizer
      Coarse-Grained Modeling of Structure and Dynamics of Biomacromolecules
    • Place of Presentation
      Telluride, USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Protential derived charge for better description of protein sliding dynamics on DNA2012

    • Author(s)
      Tsuyoshi Terakawa, Shoji Takada
    • Organizer
      揺らぎと生体機能 第6回公開シンポジウム
    • Place of Presentation
      京都テルサ(京都市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Stability and dynamics of RNA virus(T=1) studied by coarse-grained simulations2012

    • Author(s)
      Koji Ono, Naoto Hori, Shoji Takada
    • Organizer
      揺らぎと生体機能 第6回公開シンポジウム
    • Place of Presentation
      京都テルサ(京都市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Fluctuations of Transfer RNAs in the Ribosome Cavity Studied by Coarse-Grained Simulations2012

    • Author(s)
      Naoto Hori, Shoji Takada
    • Organizer
      揺らぎと生体機能第5回公開シンポジウム
    • Place of Presentation
      東大寺総合文化センター(奈良市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Transcription Factor p53 Searching Dynamics on DNA Studied by Coarse-Grained Simulation2012

    • Author(s)
      Tsuyoshi Terakawa, Shoji Takada
    • Organizer
      揺らぎと生体機能第5回公開シンポジウム
    • Place of Presentation
      東大寺総合文化センター(奈良市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 全原子計算によるキネシン-微小管間の界面構造のリファイメント2012

    • Author(s)
      金田亮, 牧野司, 富重道雄, 高田彰二
    • Organizer
      次世代ナノ統合シミュレーションソフトウェアの研究開発(ナノ統合)次世代生命体統合シミュレーションソフトウェアの研究開発(ライフ)公開シンポジウム
    • Place of Presentation
      神戸ポートアイランドセンターニチイ学館(神戸市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生体分子粗視化シミュレータCafeMolの開発と応用2012

    • Author(s)
      検崎博生, 高田彰二
    • Organizer
      次世代ナノ統合シミュレーションソフトウェアの研究開発(ナノ統合)次世代生命体統合シミュレーションソフトウェアの研究開発(ライフ)公開シンポジウム
    • Place of Presentation
      神戸ポートアイランドセンターニチイ学館(神戸市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Drug uptake in a multidrug transporter studied by coarse-grained simulations2012

    • Author(s)
      Xin-Qiu Yao, Shoji Takada
    • Organizer
      次世代ナノ統合シミュレーションソフトウェアの研究開発(ナノ統合)次世代生命体統合シミュレーションソフトウェアの研究開発(ライフ)公開シンポジウム
    • Place of Presentation
      神戸ポートアイランドセンターニチイ学館(神戸市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] A Coarse-Grained Simulation Study of Ribosome and tRNA Dynamics during Translocation2012

    • Author(s)
      Naoto Hori, Shoji Takada
    • Organizer
      Biophysical Society 56th Annual Meeting
    • Place of Presentation
      The San Diego Convention Center (USA)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mathematical modeling of apoptosis-survival signal transduction pathway and its response of cell poulation2011

    • Author(s)
      村上陽平, 高田彰二
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ligand motions coupled with protein conformational changes : Rhodopsin and a drug transporter2011

    • Author(s)
      Shoji Takada
    • Organizer
      IMS Symposium on "Recent Developments of Spectroscopy and Spatial and Temporal Hierarchical Structures in Molecular Science"
    • Place of Presentation
      National Institute for Physiological Sciences (Okazaki)(招待講演)
    • Year and Date
      2011-10-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生体分子シミュレーションによる蛋白質ゆらぎ、構造変化、機能研究2011

    • Author(s)
      高田彰二
    • Organizer
      第17回創薬情報研究会
    • Place of Presentation
      新大阪丸ビル新館(大阪市)(招待講演)
    • Year and Date
      2011-09-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-Grained Modeling of Biomolecular Systems2011

    • Author(s)
      Shoji Takada
    • Organizer
      Theorectical Chemistry Institute Seminar
    • Place of Presentation
      University of Wisconsin-Madison (USA)(招待講演)
    • Year and Date
      2011-08-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Multiscale computational approach to kinesin and F1-ATPase2011

    • Author(s)
      Shoji Takada
    • Organizer
      Telluride Science Research center meeting
    • Place of Presentation
      Telluride (USA)(招待講演)
    • Year and Date
      2011-08-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Large scale protein motions studied by multiscale simulations2011

    • Author(s)
      Shoji Takada
    • Organizer
      International workshop on multiscale characterization of biological systems : From molecules to networks
    • Place of Presentation
      Nanjin University (China)(招待講演)
    • Year and Date
      2011-06-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] 粗視化分子モデルによる生体分子機械の作動原理研究2011

    • Author(s)
      高田彰二
    • Organizer
      日本物理学会2011年秋期大会
    • Place of Presentation
      富山大学五福キャンパス(富山市)(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 特有の立体構造を取るRNAのダイナミクスに迫る-粗視化モデルによる試み-2011

    • Author(s)
      掘直人, 高田彰二
    • Organizer
      次世代バイオインフォマティクス研究会
    • Place of Presentation
      産業技術総合研究所北海道センター(札幌市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Multiscale Biomolecular Simulations of Kinesin Motors2011

    • Author(s)
      Ryo Kanada, Takeshi Kuwata, Hiroo Kenzaki, Tukasa Makino, Michio Tomishige, Shoji Takada
    • Organizer
      The 2nd international symposium on "Multi-scale Simulations of Biological and Soft Materials" (MSBSM 2011)
    • Place of Presentation
      Shiran Kaikan (Kyoto)
    • Related Report
      2011 Annual Research Report
  • [Presentation] The interface structure between kinesin and microtubule refined by all-atom MD simulations2011

    • Author(s)
      Ryo Kanada, Tsukasa Makino, Michio Tomishige, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-grained simulations of multi-nucleosome systems2011

    • Author(s)
      Hiroo Kenzaki, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] The uptake and export of drugs in a multidrug transporter studied by coarse-grained simulations2011

    • Author(s)
      Xin-Qiu Yao, Hiroo Kenzaki, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-grained molecular simulation study of ribosomal translocation dynamics2011

    • Author(s)
      Naoto Hori, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] On application of multi-scale ensemble modeling method to tumor suppressor p53 quaternary structure2011

    • Author(s)
      Tsuyoshi Terakawa, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Activation mechanism of rhodopsin elucidated by molecular dynamics simulations2011

    • Author(s)
      Fuyuki Sakai, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular dynamics simulation of pH-activated KcsA channel2011

    • Author(s)
      Atsushi Horimoto, Shoji Takada
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(姫路市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 翻訳中のリボソーム複合体とtRNAのダイナミクス-粗視化分子シミュレーション-2011

    • Author(s)
      掘直人, 高田彰二
    • Organizer
      第11回日本蛋白質科学会年会
    • Place of Presentation
      ホテル阪急エキスポパーク(吹田市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] On application of multi-scale ensemble modeling method to tumor suppressor p53 quaternary structure2011

    • Author(s)
      寺川剛, 高田彰二
    • Organizer
      第11回日本蛋白質科学会年会
    • Place of Presentation
      ホテル阪急エキスポパーク(吹田市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] ロドプシン活性過程におけるレチナールの反転2011

    • Author(s)
      坂井冬樹, 高田彰二
    • Organizer
      第11回日本蛋白質科学会年会
    • Place of Presentation
      ホテル阪急エキスポパーク(吹田市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ribosome and tRNA Dynamics during Elongation Studied by Coarse-Grained Molecular Simulations2011

    • Author(s)
      Naoto Hori, Shoji Takada
    • Organizer
      The 16th Annual Meeting of the RNA Society
    • Place of Presentation
      Kyoto international Conference Center (Kyoto)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-grained simulation of protein-DNA complex : mechanical unzipping of nucleosome2011

    • Author(s)
      Hiroo Kenzaki, Shoji Takada
    • Organizer
      The 2nd international symposium on "Multi-scale Simulations of Biological and Soft Materials" (MSBSM 2011)
    • Place of Presentation
      Shiran Kaikan (Kyoto)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coarse-grained model of RNA-protein complexes derived by multiscale simulation method2011

    • Author(s)
      Naoto Hori, Shoji Takada
    • Organizer
      The 2nd international symposium on "Multi-scale Simulations of Biological and Soft Materials" (MSBSM 2011)
    • Place of Presentation
      Shiran Kaikan (Kyoto)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 全原子シミュレーションによるキネシン-微小管間の界面構造のリファインメント2011

    • Author(s)
      金田亮, 高田彰二
    • Organizer
      バイオスーパーコンピューティングサマースクール2011
    • Place of Presentation
      兵庫県立淡路夢舞台国際会議場(淡路)
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヌクレオソームのアンジッピングシミュレーション2011

    • Author(s)
      検崎博生, 高田彰二
    • Organizer
      バイオスーパーコンピューティングサマースクール2011
    • Place of Presentation
      兵庫県立淡路夢舞台国際会議場(淡路)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Drug translocation and allosteric coupling in a multidrug transporter studied by molecular simulations2011

    • Author(s)
      Xin-Qiu Yao, Shoji Takada
    • Organizer
      17th International Biophysics Congress
    • Place of Presentation
      China National Convention Center (China)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Recent progress in multiscale modeling of biomolecular systems

    • Author(s)
      Shoji Takada
    • Organizer
      The 3rd International Workshop on "Multiscale Characterizations of Biological Systems: From Molecules to Networks
    • Place of Presentation
      BI YU YUAN, China
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 癌抑制転写因子p53はDNA上をどのように走査するか?

    • Author(s)
      寺川剛, 検崎博生, 高田彰二
    • Organizer
      天然変性蛋白質計算科学セミナー
    • Place of Presentation
      御殿場高原(静岡市)
    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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