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Molecular dynamics simulation for the destruction mechanism of amyloid fibrils by laser irradiation

Research Project

Project/Area Number 21K06118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43040:Biophysics-related
Research InstitutionNational Institutes of Natural Sciences

Principal Investigator

Okumura Hisashi  大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 准教授 (80360337)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2023: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords分子動力学シミュレーション / アミロイド線維 / 赤外線レーザー / アミロイドβペプチド / ポリアラニン / 水
Outline of Research at the Start

アミロイド線維はタンパク質が凝集してできた針状の物質で、40種類以上の病気の原因となる。最近の実験で赤外線レーザーを照射すると水分を含んだアミロイド線維は破壊されるが、乾燥したアミロイド線維は破壊されないことが示された。この結果は水が何か重要な役割を担っていることを示唆しているが、その役割は分かっていない。また、アミロイド線維を破壊するとαヘリックス構造が多く形成されることも示されているが、その理由も分かっていない。本研究では非平衡分子動力学シミュレーションによりアミロイド線維が赤外線レーザーで破壊される際の水分子の役割を解明する。αヘリックス構造が多く形成される理由も明らかにする。

Outline of Final Research Achievements

Proteins fold properly and perform essential functions for life. However, they sometimes aggregate and cause several diseases. Attempts are being made to destroy these protein aggregates by irradiating them with infrared free-electron lasers, leading to the development of new therapeutic methods. However, the mechanism by which protein aggregates are destroyed by laser irradiation has not been understood. In this study, the mechanism was elucidated by computer simulation. I also clarified which protein aggregates are easily destroyed and which protein aggregates are not easily destroyed.

Academic Significance and Societal Importance of the Research Achievements

タンパク質凝集体の引き起こす病気にはアルツハイマー病やハンチントン病、パーキンソン病など治療法が確立していない病気が多い。これらの大半の病気には対処療法しかなく、その原因を直接取り除く方法はない。赤外線レーザーを照射する方法は病気の原因に直接アタックするので、この方法が実用に至れば意義は大きい。これまでレーザー照射により病気の原因物質を除去できることは実験的に知られていたが、その理由は不明であった。これを明らかにしたのが本研究である。本研究により将来、治療に使えるかもしれない手法の理論的裏付けを与えることができた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (34 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (25 results) (of which Int'l Joint Research: 12 results,  Invited: 23 results) Book (1 results)

  • [Journal Article] Dissociation process of polyalanine aggregates by free electron laser irradiation2023

    • Author(s)
      Okumura Hisashi、Itoh Satoru G.、Zen Heishun、Nakamura Kazuhiro
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 9 Pages: e0291093-e0291093

    • DOI

      10.1371/journal.pone.0291093

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Perspective for Molecular Dynamics Simulation Studies of Amyloid-β Aggregates2023

    • Author(s)
      Okumura Hisashi
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 127 Issue: 51 Pages: 10931-10940

    • DOI

      10.1021/acs.jpcb.3c06051

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Probing protein misfolding and dissociation with an infrared free-electron laser2023

    • Author(s)
      Okumura Hisashi、Kawasaki Takayasu、Nakamura Kazuhiro
    • Journal Title

      Methods in Enzymology

      Volume: 679 Pages: 65-96

    • DOI

      10.1016/bs.mie.2022.08.047

    • ISBN
      9780323992640
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Double-Layered Structure of Amyloid-β Assemblage on GM1-Containing Membranes Catalytically Promotes Fibrillization2023

    • Author(s)
      Yagi-Utsumi Maho、Itoh Satoru G.、Okumura Hisashi、Yanagisawa Katsuhiko、Kato Koichi、Nishimura Katsuyuki
    • Journal Title

      ACS Chemical Neuroscience

      Volume: 14 Issue: 15 Pages: 2648-2657

    • DOI

      10.1021/acschemneuro.3c00192

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 超音波と赤外線レーザーによるアミロイド線維の破壊を分子動力学シミュレーションで見る2023

    • Author(s)
      奥村久士
    • Journal Title

      高圧力の科学と技術

      Volume: 33 Pages: 76-82

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation2022

    • Author(s)
      Hisashi Okumura and Satoru G. Itoh
    • Journal Title

      Molecules

      Volume: 27 Issue: 8 Pages: 2483-2483

    • DOI

      10.3390/molecules27082483

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 赤外自由電子レーザによるアミロイド線維破壊の分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Journal Title

      レーザ加工学会誌

      Volume: 29 Pages: 160-165

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of Water Molecules and Helix Structure Stabilization in the Laser-Induced Disruption of Amyloid Fibrils Observed by Nonequilibrium Molecular Dynamics Simulations.2021

    • Author(s)
      Okumura H, Itoh SG, Nakamura K, Kawasaki T.
    • Journal Title

      J. Phys. Chem. B

      Volume: in press Issue: 19 Pages: 2361-2368

    • DOI

      10.1021/acs.jpcb.0c11491

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Molecular dynamics simulation for the causative substance of Alzheimer's disease2023

    • Author(s)
      Hisashi OKUMURA
    • Organizer
      5th International Conference on Materials Research and Innovation
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Amyloid-fibril dissociation observed by nonequilibrium molecular dynamics simulation2023

    • Author(s)
      Hisashi OKUMURA
    • Organizer
      The 16th Eurasia Conference on Chemical Sciences
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Disease-related proteins studied by molecular dynamics simulations2023

    • Author(s)
      Hisashi OKUMURA
    • Organizer
      ACS Global Innovation Imperatives - 7th International Conference on Computation for Science and Technology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Key factors for aggregation and disaggregation of amyloid-β peptides revealed by molecular dynamics simulations2023

    • Author(s)
      Hisashi OKUMURA
    • Organizer
      19th International Conference of Computational Methods in Sciences and Engineering
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aggregation and disaggregation of amyloid-β peptides observed by all-atom molecular dynamics simulations2023

    • Author(s)
      Hisashi OKUMURA
    • Organizer
      The 26th International Annual Symposium on Computational Science and Engineering
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Replica-permutation and nonequilibrium molecular dynamics simulations for protein aggregates2023

    • Author(s)
      Hisashi OKUMURA
    • Organizer
      Biomolecules and Nanostructures 8
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] All-atom molecular dynamics simulations for the formation and dissociation of amyloid-β aggregates / アミロイドβ凝集体の形成と解離の全原子分子動力学シミュレーション2023

    • Author(s)
      奥村久士
    • Organizer
      第61回日本生物物理学会年会シンポジウム「Liquid-liquid phase separation and amyloid formation driven by dynamic solution environments / 動的溶液環境が駆動する生体内液液相分離とアミロイド線維化」
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 中赤外レーザーによるアミロイドβ凝集体の選択的破壊2023

    • Author(s)
      奥村久士
    • Organizer
      多元技術融合光プロセス研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] コンピュータシミュレーョンで見るアルツハイマー病原因物質の分子動画2023

    • Author(s)
      奥村久士
    • Organizer
      第32回高速分子動画オンラインセミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Generalized-ensemble and nonequilibrium molecular dynamics simulations of protein aggregates2023

    • Author(s)
      Hisashi Okumura
    • Organizer
      Asia and Pacific Conference of Theoretical and Computational Chemistry
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 病気の原因となるタンパク質の分子動力学シミュレーション2023

    • Author(s)
      奥村久士
    • Organizer
      企業研究会第36期CAMMフォーラム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Protein aggregation and disaggregation by generalized-ensemble and nonequilibrium molecular dynamics simulations2022

    • Author(s)
      Hisashi Okumura
    • Organizer
      4th International Conference on Materials Research and Innovation
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Disaggregation of amyloid-β aggregates observed by nonequilibrium molecular dynamics simulations2022

    • Author(s)
      Hisashi Okumura
    • Organizer
      18th International Conference of Computational Methods in Sciences and Engineering
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体機能に重要な分子の全原子分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Organizer
      Biothermology Workshop 2022
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] アミロイド線維の非平衡分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Organizer
      山形大学理学部 離散数理セミナー
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 非平衡分子動力学シミュレーションで見る極限環境下におけるアミロイド線維破壊2022

    • Author(s)
      奥村久士
    • Organizer
      第63回高圧討論会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] アミロイドβペプチド凝集体の非平衡分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Organizer
      Mie Meeting of Quantum Science
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 病気に関係する生体分子の分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Organizer
      生理学研究所ネットワーク型研究加速事業報告会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 新型コロナウイルスの増殖とアルツハイマー病の発症に関するタンパク質の分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Organizer
      スーパーコンピュータワークショップ2021
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 分子動力学シミュレーションで見る赤外自由電子レーザーによるアミロイド線維の破壊2022

    • Author(s)
      奥村久士
    • Organizer
      第35回日本放射光学会年会・放射光科学合同シンポジウム 企画講演:赤外自由電子レーザーによる物質研究の現状と未来展望
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] アミロイドβペプチドの凝集と解離の分子動力学シミュレーション2022

    • Author(s)
      奥村久士
    • Organizer
      第59回日本生物物理学会年会シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Molecular dynamics simulation of disease-related biomolecules2021

    • Author(s)
      Hisashi Okumura
    • Organizer
      2nd International Conference on Materials Research and Innovation
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of water molecules and helix-structure stabilization in the laser-induced disruption of amyloid fibrils observed by nonequilibrium molecular dynamics simulations2021

    • Author(s)
      Hisashi Okumura
    • Organizer
      Skype seminar
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Nonequilibrium molecular dynamics simulation to reveal a role of water molecules in laser-induced disruption of amyloid brils2021

    • Author(s)
      Hisashi Okumura, Satoru G. Itoh, Kazuhiro Nakamura, Takayasu Kawasaki
    • Organizer
      XXXI I IUPAP Conference on Computational Physics (CCP2021)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 分子動力学法で調べた赤外自由電子レーザーによる アミロイド線維の破壊とヘリックス構造の安定化2021

    • Author(s)
      奥村久士,伊藤暁, 中村和裕, 川崎平康
    • Organizer
      第35回分子シミュレーション討論会
    • Related Report
      2021 Research-status Report
  • [Book] Probing protein misfolding and dissociation with an infrared free-electron laser, Methods in Enzymology, Volume 679 "Integrated Methods in Protein Biochemistry: Part B", Chap. 32023

    • Author(s)
      Hisashi Okumura, Takayasu Kawasaki, and Kazuhiro Nakamura
    • Total Pages
      32
    • Publisher
      Academic Press
    • ISBN
      9780323992640
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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