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Theoretical Analysis and Rational Design of Catalytic Activity of Flexible Molecules

Planned Research

Project AreaScience on Function of Soft Molecular Systems by Cooperation of Theory and Experiment
Project/Area Number 25104004
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

HAYASHI Shigehiko  京都大学, 理学研究科, 教授 (70402758)

Project Period (FY) 2013-06-28 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥50,830,000 (Direct Cost: ¥39,100,000、Indirect Cost: ¥11,730,000)
Fiscal Year 2017: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2016: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2015: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2014: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2013: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Keywords分子シミュレーション / 量子化学計算 / 分子動力学法 / ハイブリッド法 / シグナル伝達タンパク質 / 光受容体タンパク質 / 機能性有機分子集合体 / 酵素活性 / QM/MM 法 / 分子機能 / 酵素反応 / 超分子 / 膜輸送体 / イオン結合タンパク質 / 光受容タンパク質 / ハイブリッド QM/MM 法 / 光遺伝学 / 自己組織化分子 / 発光タンパク質 / 電子伝達タンパク質 / モータータンパク質 / 酵素設計
Outline of Final Research Achievements

Conformational flexibility of complex molecular systems plays an essential role in their molecular functions. For example, conformational flexibility of biomolecules furnishes them with high molecular recognition and catalytic activity, allowing them to convert and mediate various information and energy forms necessary for biological activities. In the present study, we elucidated in atomic details the role of conformational flexibility in molecular functions of biological molecules and functional organic molecular assemblies by using a novel molecular simulation approach developed recently by us, QM/MM RWFE-SCF, which is capable of describing correlations between highly complex chemical reactions and large conformational changes of extended molecular systems. Furthermore, we carried out analysis of oncogenic mutants of a signaling protein complex and design of color variants of photo-receptor proteins with the QM/MM RWFE-SCF method.

Report

(6 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (41 results)

All 2017 2016 2015 2014 2013

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (25 results) (of which Int'l Joint Research: 9 results,  Invited: 25 results)

  • [Journal Article] Atomistic modeling of alternating access of a mitochondrial ADP/ATP membrane transporter with molecular simulations2017

    • Author(s)
      Koichi Tamura and Shigehiko Hayashi*
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0181489-e0181489

    • DOI

      10.1371/journal.pone.0181489

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A polyaromatic nanocapsule as a sucrose receptor in water2017

    • Author(s)
      Masahiro Yamashina, Munetaka Akita, Taisuke Hasegawa, Shigehiko Hayashi, and Michito Yoshizawa*
    • Journal Title

      Science Advances

      Volume: 3 Issue: 8

    • DOI

      10.1126/sciadv.1701126

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] QM/MM geometry optimization on extensive free-energy surfaces for examination of enzymatic reactions and design of novel functional properties of proteins2017

    • Author(s)
      Shigehiko Hayashi*, Yoshihiro Uchida, Taisuke Hasegawa, Masahiro Higashi, Takahiro Kosugi, and Motoshi Kamiya
    • Journal Title

      Annual Review of Physical Chemistry

      Volume: 63 Issue: 1 Pages: 135-154

    • DOI

      10.1146/annurev-physchem-052516-050827

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ハイブリッド分子シミュレーションによるロドプシン光受容体の分子機能の理解と設計2017

    • Author(s)
      林 重彦
    • Journal Title

      医学のあゆみ - 第5土曜特集号「生命現象を観る-革新的な構造生命科学が観せてくれる世界」

      Volume: 262 Pages: 552-558

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Photoactivation intermediates of a G-protein coupled receptor rhodopsin investigated by a hybrid molecular simulation.2017

    • Author(s)
      Motoshi Kamiya and Shigehiko Hayashi*
    • Journal Title

      Journal of Physical Chemistry B

      Volume: 121 Issue: 15 Pages: 3842-3852

    • DOI

      10.1021/acs.jpcb.6b13050

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] X-ray crystallographic structure of thermophilic rhodopsin: implications for high thermal stability and optogenetic function2016

    • Author(s)
      Tsukamoto T, Mizutani K, Hasegawa T, Takahashi M, Honda N, Hashimoto N, Shimono K, Yamashita K, Yamamoto M, Miyauchi S, Takagi S, Hayashi S, Murata T, Sudo Y.
    • Journal Title

      J. Biol. Chem.

      Volume: in press Issue: 23 Pages: 12223-12232

    • DOI

      10.1074/jbc.m116.719815

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Atomistic design of microbial opsin-based blue-shifted optogenetics tools2015

    • Author(s)
      Kato HE, Kamiya M, Sugo S, Ito J, Taniguchi R, Orito A, Hirata K, Inutsuka A,Yamanaka A, Maturana AD, Ishitani R, Sudo Y, Hayashi S, Nureki O
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 7177-7177

    • DOI

      10.1038/ncomms8177

    • NAID

      120005745621

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Linear response path following: a molecular dynamics method to simulate global conformational changes of protein upon ligand binding2015

    • Author(s)
      Koichi Tamura and Shigehiko Hayashi
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 11 Issue: 7 Pages: 2900-2917

    • DOI

      10.1021/acs.jctc.5b00120

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular dynamics of channelrhodopsin at the early stages of channel opening2015

    • Author(s)
      Mizuki Takemoto, Hideaki E. Kato, Michio Koyama, Jumpei Ito, Motoshi Kamiya, Shigehiko Hayashi, Andres D. Maturana, Karl Deisseroth, Ryuichiro Ishitani, and Osamu Nureki
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 6 Pages: 0131094-0131094

    • DOI

      10.1371/journal.pone.0131094

    • NAID

      120005947158

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular mechanism of wide photoabsorption spectral shifts of color variants of human cellular retinol binding protein II2015

    • Author(s)
      Cheng Cheng, Motoshi Kamiya, Yoshihiro Uchida, and Shigehiko Hayashi
    • Journal Title

      Journal of the American Chemical Society

      Volume: 137 Issue: 41 Pages: 13362-13370

    • DOI

      10.1021/jacs.5b08316

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of bulk water environment in regulation of functional hydrogen-bond network in photoactive yellow protein2015

    • Author(s)
      Koichi Tamura and Shigehiko Hayashi
    • Journal Title

      Journal of Physical Chemistry B

      Volume: 119 Issue: 51 Pages: 15537-15549

    • DOI

      10.1021/acs.jpcb.5b07555

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Converting a light-driven proton pump into a light-gated proton channel2015

    • Author(s)
      K. Inoue, T. Tsukamoto, K. Shimono, Y. Suzuki, S. Miyauchi, S. Hayashi, H. Kandori, Y. Sudo*
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 9 Pages: 3291-3299

    • DOI

      10.1021/ja511788f

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Silencing neurons with light2014

    • Author(s)
      Shigehiko Hayashi
    • Journal Title

      Science

      Volume: 344 Issue: 6182 Pages: 369-370

    • DOI

      10.1126/science.1253616

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Theoretical study on excited states of bacteriochlorophyll a in solutions with density functional assessment2014

    • Author(s)
      Masahiro Higashi, Takahiro Kosugi, Shigehiko Hayashi, and Shinji Saito
    • Journal Title

      Journal of Physical Chemistry B

      Volume: 118 Issue: 37 Pages: 10906-10918

    • DOI

      10.1021/jp507259g

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Key Chemical Factors of Arginine Finger Catalysis of F1-ATPase Clarified by an Unnatural Amino Acid Mutation2014

    • Author(s)
      Yukawa A, Iino R, Watanabe R, Hayashi S and Noji H
    • Journal Title

      Biochemistry

      Volume: 54 Issue: 2 Pages: 472-480

    • DOI

      10.1021/bi501138b

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Facile Catch and Release of Fullerenes Using a Photoresponsive Molecular Tube2013

    • Author(s)
      N. Kishi, M. Akita, M. Kamiya, S. Hayashi, H. -F. Hsu, M. Yoshizawa
    • Journal Title

      Journal of the Arnerican Chemical Society

      Volume: 135 Issue: 35 Pages: 12976-12979

    • DOI

      10.1021/ja406893y

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 超分子カプセルの分子内包能と動的挙動2017

    • Author(s)
      林 重彦、吉沢道人
    • Organizer
      日本化学会 第97春季年会 シンポジウム「複雑系のための分子科学―理論、計測、合成の連携で拓く柔らかな分子の新機能」
    • Place of Presentation
      日吉・神奈川
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Understanding and designing color variants of retinal binding proteins by molecular simulations2017

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      253rd American Chemical Society National Meeting (San Francisco, USA)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Understanding and designing color variants of retinal binding proteins by molecular simulations2017

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Telluride Science Research Center Workshop on “Protein Dynamics” (Telluride, USA)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2016

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Japan-France-Spain Joint-Symposium on Theoretical and Computational Science of Complex Systems
    • Place of Presentation
      京都
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2016

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      The 16th KIAS Conference on Protein Structure and Function
    • Place of Presentation
      ソウル・韓国
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 柔らかいタンパク質の分子機能理解と設計2016

    • Author(s)
      林 重彦
    • Organizer
      第10回分子科学討論会
    • Place of Presentation
      神戸・兵庫
    • Year and Date
      2016-09-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2016

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      IAS Focused Program on “Molecular Machines of Life: Simulations Meets Experiment”
    • Place of Presentation
      香港・中国
    • Year and Date
      2016-05-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Understanding and designing color variants of retinal biding proteins by molecular simulations2015

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Pacifichem2015 Symposium “Chemistry and Applications of Retinal Proteins: From Microbes to Humans”
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2015-12-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2015

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Pacifichem2015 Symposium “Interplay between Chemistry and Dynamics in Biomolecular Machines”
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2015-12-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of Bound Water Molecules Inside Proteins in Their Functional Processes2015

    • Author(s)
      林 重彦
    • Organizer
      日本生物物理学会・シンポジウム “ポンプ、酵素、モーター、機能の鍵:pKa”
    • Place of Presentation
      金沢・石川
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2015

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      IUPAC-2015 45th World Chemistry Congress
    • Place of Presentation
      釜山・韓国
    • Year and Date
      2015-08-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 柔らかいタンパク質の分子機能の理解と設計2015

    • Author(s)
      林 重彦
    • Organizer
      第 12 回 AMO 討論会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Atomistic Understanding and Design of Microbial Opsin-based Optogenetics Tools2015

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Albany 2015: Conversation 19
    • Place of Presentation
      Albany, USA
    • Year and Date
      2015-06-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] タンパク質の pKa 制御とプロトン能動輸送の分子機構2015

    • Author(s)
      林 重彦
    • Organizer
      分子研研究会「膜タンパク質内部のプロトン透過を考える」
    • Place of Presentation
      岡崎・愛知
    • Year and Date
      2015-04-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2015

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      4th Indo-German Meeting on Modeling of Chemical and Biological Reactivity (MCBR4)
    • Place of Presentation
      Heidelberg, Germany
    • Year and Date
      2015-02-23 – 2015-02-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 柔らかいタンパク質の分子機能の理解と設計2015

    • Author(s)
      林 重彦
    • Organizer
      理研シンポジウム「生体分子系量子化学計算の最前線」
    • Place of Presentation
      和光・埼玉
    • Year and Date
      2015-01-22 – 2015-01-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 柔らかいタンパク質の分子機能の理解と設計2014

    • Author(s)
      林 重彦
    • Organizer
      CBI 学会 2014 年大会 プレナリーレクチャー
    • Place of Presentation
      東京
    • Year and Date
      2014-10-28 – 2014-10-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Understanding and Designing Color Variants of Retinal Biding Proteins by Molecular Simulations2014

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      16th International Conference on Retinal Proteins
    • Place of Presentation
      長浜・滋賀
    • Year and Date
      2014-10-05 – 2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 柔らかいタンパク質の分子機能の理解と設計2014

    • Author(s)
      林 重彦
    • Organizer
      第 14 回蛋白質科学会年会 公募型シンポジウム
    • Place of Presentation
      横浜・神奈川
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Catalytic mechanism of NTPases2014

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Tokyo ATPase Workshop
    • Place of Presentation
      東京
    • Year and Date
      2014-06-02 – 2014-06-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2014

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      Les Houches-TSRC Workshop on Protein Dynamics
    • Place of Presentation
      Les Houches, France
    • Year and Date
      2014-05-18 – 2014-05-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2014

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      CRC-EC Joint Symposium on Chemical Theory on Complex System
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 柔らかいタンパク質の分子機能の理解と設計2014

    • Author(s)
      林 重彦
    • Organizer
      自然科学研究機構計算科学研究センタースーパーコンピュータワークショップ 2014「計算化学の最新の成果と展開」
    • Place of Presentation
      岡崎・愛知
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 酵素機能における分子の柔らかさの役割2014

    • Author(s)
      林 重彦
    • Organizer
      日本化学会第 94 春季年会中長期テーマシンポジウム「複雑系のための分子科学-理論研究によるアプローチ」
    • Place of Presentation
      名古屋・愛知
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Crucial Role of Protein Flexibility in Enzymatic Catalysis2013

    • Author(s)
      Shigehiko Hayashi
    • Organizer
      3rd International Conference on Molecular Simulations
    • Place of Presentation
      神戸・兵庫
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-07-10   Modified: 2019-07-29  

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