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Theoretical study on transition path search algorithms in complex biomolecular systems

Research Project

Project/Area Number 16KT0054
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Transition State Control
Research InstitutionKyoto University

Principal Investigator

TAKADA Shoji  京都大学, 理学研究科, 教授 (60304086)

Project Period (FY) 2016-07-19 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords計算生物物理 / 生体分子シミュレーション / 遷移経路探索 / マルコフ状態モデル / マルコフ状態モデリング / ヌクレオソームスライディング / ストリング法
Outline of Final Research Achievements

We developed and implemented algorithms that can characterize large-scale structural changes in large-biomolecular complexes. Then, the methods are applied to biological problems, in this case, nucleosome structural dynamics.
First, we investigated thermally-driven spontaneous and ATP-dependent chromatin remodeler-driven nucleosome sliding processes. For the purpose, utilizing our own coarse-grained molecular dynamics methods, we could perform complete transition pathways analysis via Markov-state-modeling. In addition, we realized free energy landscape of nucleosome self-organization, again via Markov state modeling, from which we obtained detailed and salt-concentration dependent nucleosome formation/disassembly pathways.

Academic Significance and Societal Importance of the Research Achievements

ヌクレオソーム構造・動態は、近年のクロマチン研究・エピゲノム研究に関連して盛んに研究がおこなわれている。大部分は実験研究であるが、本研究は実験データに基づきながら分子動態を可視化することに成功しており、ヌクレオソーム動態にユニークな視点を与えた。
それを可能にした要因は、独自の粗視化分子シミュレーション技法と、マルコフ状態モデリングの組合せである。この方法は複雑分子系についてその遷移状態を詳細に解析する方法として強力なものであるといえる。同時に、他の研究者の利用に資するために、開発し研究に利用したシミュレーションソフトウエアCafeMolのソースコードをすべて公開している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (31 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results)

  • [Int'l Joint Research] Johns Hopkins(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Interactions of HP1 bound to H3K9me3 di-nucleosome by molecular simulations and biochemical assays2018

    • Author(s)
      Watanabe S, Mishima Y, Shimizua M, Suetake I*, Takada S*
    • Journal Title

      Biophysical J.

      Volume: 114 Issue: 10 Pages: 2336-2351

    • DOI

      10.1016/j.bpj.2018.03.025

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic and Structural Modeling of the Specificity in Protein?DNA Interactions Guided by Binding Assay and Structure Data2018

    • Author(s)
      Cheng Tan and Shoji Takada
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 14 (7) Issue: 7 Pages: 3877-3889

    • DOI

      10.1021/acs.jctc.8b00299

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chromatin remodelers couple inchworm motion with twist-defect formation to slide nucleosomal DNA2018

    • Author(s)
      Giovanni B. Brandani and Shoji Takada
    • Journal Title

      PLoS Computational Biology

      Volume: 14(11) Issue: 11 Pages: e1006512-e1006512

    • DOI

      10.1371/journal.pcbi.1006512

    • NAID

      120006540190

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA sliding in nucleosomes via twist defect propagation revealed by molecular simulations2018

    • Author(s)
      Brandani Giovanni B、Niina Toru、Tan Cheng、Takada Shoji
    • Journal Title

      Nucleic Acids Research

      Volume: 46 Issue: 6 Pages: 2788-2801

    • DOI

      10.1093/nar/gky158

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstruction of Atomistic Structures from Coarse-Grained Models for Protein?DNA Complexes2018

    • Author(s)
      Shimizu Masahiro、Takada Shoji
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 14 Issue: 3 Pages: 1682-1694

    • DOI

      10.1021/acs.jctc.7b00954

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allosteric conformational change cascade in cytoplasmic dynein revealed by structure-based molecular simulations2017

    • Author(s)
      Kubo Shintaroh、Li Wenfei、Takada Shoji
    • Journal Title

      PLOS Computational Biology

      Volume: 13 Issue: 9 Pages: e1005748-e1005748

    • DOI

      10.1371/journal.pcbi.1005748

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations2017

    • Author(s)
      Niina Toru、Brandani Giovanni B.、Tan Cheng、Takada Shoji
    • Journal Title

      PLOS Computational Biology

      Volume: 13 Issue: 12 Pages: e1005880-e1005880

    • DOI

      10.1371/journal.pcbi.1005880

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Near-atomic structural model for bacterial DNA replication initiation complex and its functional insights2016

    • Author(s)
      Masahiro Shimizu, Yasunori Noguchi, Yukari Sakiyama, Hironori Kawakami, Tsutomu Katayama, and Shoji Takada
    • Journal Title

      Proceedings of the National Academy of Sciences USA

      Volume: 113 Issue: 50

    • DOI

      10.1073/pnas.1609649113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Histone acetylation dependent energy landscapes in tri-nucleosome revealed by residue-resolved molecular simulations2016

    • Author(s)
      Le Chang and Shoji Takada
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1

    • DOI

      10.1038/srep34441

    • NAID

      120005850270

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics2016

    • Author(s)
      Cheng Tan, Tsuyoshi Terakawa, and Shoji Takada
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 138 Issue: 27 Pages: 8512-8522

    • DOI

      10.1021/jacs.6b03729

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] On the ATP binding site of the ε subunit from bacterial F-type ATP synthases2016

    • Author(s)
      Alexander Krah, and Shoji Takada
    • Journal Title

      Biochimica et Biophysica Acta - Bioenergetics

      Volume: 1857 Issue: 4 Pages: 332-340

    • DOI

      10.1016/j.bbabio.2016.01.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Coarse-Grained Force Field for Molecular Simulations of Lipid-Protein System2018

    • Author(s)
      Diego Ugarte, Shoji Takada
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フリッパーゼ作動機構解明に向けた糖鎖付加脂質の動態解析と粗視化モデリング2018

    • Author(s)
      村田隆、新稲亮、高田彰二
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 転写開始前複合体PIC形成とDNA開裂の粗視化分子シミュレーション研究2018

    • Author(s)
      篠元輝, 清水将裕, 久保進太郎, 新稲亮, 高田彰二
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanism of Biomolecular Dynamics and Function Revealed by Multiscale Physics2018

    • Author(s)
      Cheng Tan, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Investigating Genome Organization and Regulation with Coarse-Grained Molecular Simulations2018

    • Author(s)
      Cheng Tan, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Implicit Solvent Coarse-Grained Lipid Model for Molecular Simulations of Multicomponent Membrane Systems2018

    • Author(s)
      Diego Ugarte, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Flipping mechanisms of bacterial flippase Pg1K studied by all-atom and coarse grained simulations2018

    • Author(s)
      Yutaka Murata, Toru Niina, Shoji Takad
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Opening in Transcription Initiation Complex Studied by Coarse-grained Molecular Simulation2018

    • Author(s)
      Genki Shino, Masahiro Shimizu, Shintaro Kubo, Toru Niina, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] How Toll-like receptor 4 dimerization is activated in lipid raft studied by molecular simulations2018

    • Author(s)
      Manami Ikeda, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mesoscopic Molecular Simulation for Self-assembly of the Postsynaptic Density Proteins2018

    • Author(s)
      Slevin Ohama Hana, Ugarte Diego, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Distinct binding of nuclear proteins to non B-type DNA studied by molecular simulation2018

    • Author(s)
      Mami Saito, Shoji Takada
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Coarse-grained molecular simulations for giant protein-DNA complexes2017

    • Author(s)
      Shoji Takada
    • Organizer
      American Physical Society Metting, New Orleans March 2017
    • Place of Presentation
      New Orleans(USA)
    • Year and Date
      2017-03-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Protein folding and misfolding studied by molecular simulations2017

    • Author(s)
      Shoji Takada
    • Organizer
      International IPR Seminar “New Frontiers in Protein Misfolding and Aggregation”
    • Place of Presentation
      Institute for Protein Research(Osaka)
    • Year and Date
      2017-01-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Dynamics of nucleosomes and transcription factors studied by molecular simulations2017

    • Author(s)
      Shoji Takada
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] A New Coarse-Grained Lipid Model for the Study of Lipid-Membrane Protein Systems2017

    • Author(s)
      Diego Ugarte, Shoji Takada
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Sequence Dependent Spontaneous Nucleosome Slidings Revealed by Molecular Dynamics Simulation2017

    • Author(s)
      Toru Niina, Giovanni Brandani, Cheng Tan, Shoji Takada
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] In vitro versus in vivo protein folding studied by molecular simulations2017

    • Author(s)
      Shoji Takada
    • Organizer
      Nobel Symposium on Protein Folding: From Mechanisms to Impact on Cells
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 細菌DNA複製開始複合体の近原子構造モデルと機能解析2016

    • Author(s)
      清水将裕、野口泰徳、﨑山友香里、川上広宣、片山勉、高田彰二
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Multiscale Modeling of Flexible Biomolecular Complex2016

    • Author(s)
      Shoji Takada
    • Organizer
      4th International Conference on Molecular Simulation (ICMS 2016)
    • Place of Presentation
      Shanghai(China)
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2016-07-20   Modified: 2023-03-08  

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