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2015 Fiscal Year Annual Research Report

拡張アンサンブル法による蛋白質への小分子結合機構の研究

Research Project

Project/Area Number 25247071
Research InstitutionNagoya University

Principal Investigator

岡本 祐幸  名古屋大学, 理学(系)研究科(研究院), 教授 (70185487)

Project Period (FY) 2013-04-01 – 2018-03-31
Keywords生体系 / 蛋白質 / 分子シミュレーション / 拡張アンサンブル法 / 自由エネルギー計算 / 量子効果
Outline of Annual Research Achievements

本年度は、蛋白質への小分子結合機構の研究のモデル系として、小分子同士の結合を量子効果を化学結合ができたり解離したりできる、量子効果を取り入れた拡張アンサンブルシミュレーション法の開発を行った。これまでは古典系を扱ってきたが、今回、初めて量子効果を取り入れた。量子効果としては、密度汎関数法を近似する、強結合近似密度汎関数法(Density Functional Tight Binding: DFTB)を採用した。また、拡張アンサンブル法としては、レプリカ交換傘サンプル法(Replica-Exchange Umbrella Sampling: REUS)を採用した。手法開発とプログラム作成を終えた後、テスト系として、まず、マロンアルデヒドの分子内プロトン移動に関する平均力ポテンシャル(自由エネルギー)を計算し、手法の妥当性を確認した。次に、小分子同士の結合過程を調べるために、4つのフタロニトリル分子と鉄原子1個の系にREUS/DFTBを適用し、1個のフタロシアニン分子が形成されることを示すことに初めて成功した。これによって、小分子が蛋白質に結合するときに、化学結合ができたり、壊れたりするような過程を含む場合でも、REUS/DFTBによって、量子効果を取り入れた拡張アンサンブルシミュレーションが実行できるようになった。本手法は小分子系で広く使われているDFTB+や生体分子系で広く使われているAMBERという2つ計算プログラムにおいて開発されたものであり、意義が大きい。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

昨年度に完成した、古典力学に基づく、2次元レプリカ交換法(レプリカ交換傘サンプル法とレプリカ交換洋室焼き戻し法の合体)による拡張アンサンブルドッキングシミュレーション法に続き、本年度は、更に、強結合近似密度汎関数法による量子効果を取り入れた拡張アンサンブル法の開発に成功した。順調に進展していると言える。

Strategy for Future Research Activity

研究が順調に進展しており、主な手法開発が山場を越えたので、後は、様々な具体例において、蛋白質への小分子の拡張アンサンブルドッキングシミュレーションを実行して、小分子結合機構を詳しく研究していく。

  • Research Products

    (26 results)

All 2016 2015

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Acknowledgement Compliant: 7 results) Presentation (14 results) (of which Int'l Joint Research: 11 results,  Invited: 14 results) Book (1 results)

  • [Journal Article] 分子動力学シミュレーションによる医学・創薬に向けたタンパク質の構造解析2016

    • Author(s)
      榮 慶丈, 西川 直宏,塚本 修一朗,鈴木 孝禎,岡本 祐幸
    • Journal Title

      薬学雑誌

      Volume: 136 Pages: 113-120

    • DOI

      10.1248/yakushi.15-00230-4

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Equilibrium Molecular Thermodynamics from Kirkwood Sampling2015

    • Author(s)
      S. Somani, Y. Okamoto, A.J. Ballard, and D.J. Wales
    • Journal Title

      Journal of Physical Chemistry B

      Volume: 119 Pages: 6155-6169

    • DOI

      10.1021/acs.jpcb.5b01800

    • Peer Reviewed
  • [Journal Article] Predictions of tertiary structures of a-helical membrane proteins by replica-exchange method with consideration of helix deformations2015

    • Author(s)
      R. Urano, H. Kokubo, and Y. Okamoto
    • Journal Title

      Journal of the Physical Society of Japan

      Volume: 84 Pages: 084802

    • DOI

      10.7566/JPSJ.84.084802

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Designed-walk replica-exchange method for simulations of complex systems2015

    • Author(s)
      R. Urano and Y. Okamoto
    • Journal Title

      Computer Physics Communications

      Volume: 196 Pages: 380-383

    • DOI

      10.1016/j.cpc.2015.07.007

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Deterministic replica-exchange method without pseudo random numbers for simulations of complex systems2015

    • Author(s)
      R. Urano and Y. Okamoto
    • Journal Title

      Computer Physics Communications

      Volume: 197 Pages: 128- 135

    • DOI

      10.1016/j.cpc.2015.08.020

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Observation of helix associations for insertion of a retinal molecule and distortions of helix structures in bacteriorhodopsin2015

    • Author(s)
      R. Urano and Y. Okamoto
    • Journal Title

      Journal of Chemical Physics

      Volume: 143 Pages: 235101

    • DOI

      10.1063/1.4935964

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Replica-exchange molecular dynamics simulation for understanding the initial process of amyloid peptide aggregation2015

    • Author(s)
      N. Nishikawa, P.H. Nguyen, P. Derreumaux, and Y. Okamoto
    • Journal Title

      Molecular Simulation

      Volume: 41 Pages: 1041-1044

    • DOI

      10.1080/08927022.2014.938445

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Conformational search simulations of Trp-cage using genetic crossover2015

    • Author(s)
      Yoshitake Sakae, Tomoyuki Hiroyasu, Mitsunori Miki, Katsuya Ishii & Yuko Okamoto
    • Journal Title

      Moleculer Simulation

      Volume: 41 Pages: 1045-1049

    • DOI

      10.1080/08927022.2015.1016937

    • Peer Reviewed
  • [Journal Article] Conformational Dynamics of Oligosaccharides Characterized by Paramagnetism-Assisted NMR Spectroscopy in Conjunction with Molecular Dynamics Simulation2015

    • Author(s)
      Ying Zhang, Takumi Yamaguchi, Tadashi Satoh, Maho Yagi-Utsumi, Yukiko Kamiya, Yoshitake Sakae, Yuko Okamoto, and Koichi Kato
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: 842 Pages: 217-230

    • DOI

      10.1007/978-3-319-11280-0_14

    • Peer Reviewed
  • [Journal Article] Molecular Dynamics Simulations to Clarify the Concentration Dependency of Protein Aggregation2015

    • Author(s)
      N. Nishikawa, Y. Sakae, and Y. Okamoto
    • Journal Title

      JPS Conference Proceedings

      Volume: 5 Pages: 011020

    • DOI

      10.7566/JPSCP.5.011020

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Editorial: ICMS2013 Special Issue: Proceedings of the 3rd International Conference on Molecular Simulation2015

    • Author(s)
      Y. Okamoto
    • Journal Title

      Molecular Simulation

      Volume: 41 Pages: 779

    • DOI

      10.1080/08927022.2015.1048075

  • [Presentation] Generalized-ensemble simulations of complex systems2016

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      2016 NCTS March Workshop on Critical Phenomena and Complex Systems
    • Place of Presentation
      Hsinchu, Taiwan
    • Year and Date
      2016-03-28 – 2016-03-29
    • Int'l Joint Research / Invited
  • [Presentation] Protein dynamics studied by generalized-ensemble simulations2016

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      The 251st American Chemical Society National Meeting Symposium under the Computers in Chemistry (COMP) Division “30 Years of Protein Dynamics in Silico”
    • Place of Presentation
      San Diego, California, U.S.A.
    • Year and Date
      2016-03-13 – 2016-03-17
    • Int'l Joint Research / Invited
  • [Presentation] 拡張アンサンブル法による複雑系の計算機シミュレーション2016

    • Author(s)
      岡本祐幸
    • Organizer
      国際高等研究所 研究プロジェクト 「分子基盤に基づく生体機能ネットワークとダイナミクスの解明」第5回研究会
    • Place of Presentation
      木津川市、日本
    • Year and Date
      2016-02-18 – 2016-02-19
    • Invited
  • [Presentation] Enhanced sampling methods for exascale computational chemistry2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      The 2015 International Chemical Congress of Pacific Basin Societies (PACIFICHEM2015)
    • Place of Presentation
      Honolulu, Hawaii, U.S.A.
    • Year and Date
      2015-12-15 – 2015-12-20
    • Int'l Joint Research / Invited
  • [Presentation] Generalized-ensemble algorithms for enhanced configurational sampling2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      Algorithms in Structural Bioinformatics: Sampling in Biomacromolecular Systems (AlgoSB Winter School - 2015)
    • Place of Presentation
      Cargese, Corsica, France
    • Year and Date
      2015-11-29 – 2015-12-04
    • Int'l Joint Research / Invited
  • [Presentation] 拡張アンサンブル法による量子化学シミュレーション2015

    • Author(s)
      岡本祐幸
    • Organizer
      分子研研究会「理論計算分子科学ワークショップ」
    • Place of Presentation
      岡崎市、日本
    • Year and Date
      2015-10-22 – 2015-10-22
    • Invited
  • [Presentation] Generalized-ensemble simulations of classical and quantum molecular systems2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      The 6th Japan-Czech-Slovak International Symposium for Theoretical Chemistry
    • Place of Presentation
      Smolenice, Slovakia
    • Year and Date
      2015-10-11 – 2015-10-15
    • Int'l Joint Research / Invited
  • [Presentation] Generalized-ensemble simulations2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      Hands-on Workshop on Computational Biophysics at Okazaki
    • Place of Presentation
      Okazaki, Japan
    • Year and Date
      2015-09-09 – 2015-09-11
    • Int'l Joint Research / Invited
  • [Presentation] 古典系および量子系の拡張アンサンブルシミュレーション2015

    • Author(s)
      岡本祐幸
    • Organizer
      スーパーコンピュータワークショップ
    • Place of Presentation
      岡崎市、日本
    • Year and Date
      2015-09-07 – 2015-09-08
    • Invited
  • [Presentation] Generalized-ensemble simulations of complex systems2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      2015 NCTS International Workshop on Critical Phenomena and Complex Systems
    • Place of Presentation
      Hsinchu, Taiwan
    • Year and Date
      2015-08-15 – 2015-08-17
    • Int'l Joint Research / Invited
  • [Presentation] Generalized-ensemble algorithms for calculations of ligand binding affinity2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      BIRS Workshop: Free-Energy Calculations. A Mathematical Perspective
    • Place of Presentation
      Oaxaca, Mexico
    • Year and Date
      2015-07-19 – 2015-07-24
    • Int'l Joint Research / Invited
  • [Presentation] Generalized-ensemble algorithms for enhanced sampling and free energy calculations2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      Summer Snowmass Biophysics Workshop Free Energy Calculations: Three Decades of Adventure in Chemistry and Biophysics
    • Place of Presentation
      Snowmass, Colorado, U.S.A.
    • Year and Date
      2015-07-05 – 2015-07-09
    • Int'l Joint Research / Invited
  • [Presentation] Efficient sampling methods for identifying transition states2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      TSRC Workshop on the Chemistry and Dynamics in Complex Environments (CHEM-DiCE)
    • Place of Presentation
      Telluride, Colorado, U.S.A.
    • Year and Date
      2015-06-23 – 2015-06-26
    • Int'l Joint Research / Invited
  • [Presentation] Efficient sampling methods for complex systems2015

    • Author(s)
      Yuko OKAMOTO
    • Organizer
      The 19th International Annual Symposium on Computational Science and Engineering (ANSCSE19)
    • Place of Presentation
      Ubon Ratchathani, Thailand
    • Year and Date
      2015-06-17 – 2015-06-19
    • Int'l Joint Research / Invited
  • [Book] Molecular Science of Fluctuations Toward Biological Functions2016

    • Author(s)
      M. Terazima, M. Kataoka, R. Ueoka, and Y. Okamoto (eds.)
    • Total Pages
      270
    • Publisher
      Springer

URL: 

Published: 2017-01-06   Modified: 2023-03-16  

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