Structure modeling and functional analysis of rotary motor state proteins based on mutational information

• Project/Area Number: 23370066
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biophysics
• Research Institution: The University of Tokyo
• Principal Investigator: KITAO Akio 東京大学, 分子細胞生物学研究所, 准教授 (30252422)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 生体膜 / 受容体 / チャネル / 立体構造モデリング / チャンネル

Outline of Final Research Achievements

We have conducted a structure modeling of the transmembrane part of the stator complex MotA/B in the flagellar motor of Escherichia coli and investigated the proton permeation process. We found that hydrophobic channels are formed in MotA/B and protons are transported as hydronium ions through the channel. We also found that protonation/deprotonation of Asp32 can induce a ratchet motion of the cytoplasmic domain. This research result is now in press in the Proc Natl Acad Sci USA.

Research Products

• [Journal Article] Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton. (2015)
  • Author(s): Taki Sakai, Yotaro Matsumoto, Minoru Ishikawa, Kazuyuki Sugita, Yuichi Hashimoto, Nobuhiko Wakai, Akio Kitao, Era Morishita, Chikashi Toyoshima, Tomoatsu Hayashi, Tetsu Akiyama
  • Journal Title: Bioorg Med Chem. Volume: 23 Issue: 2 Pages: 328-339
  • DOI: 10.1016/j.bmc.2014.11.027
  • Peer Reviewed / Open Access
• [Journal Article] TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2 (2014)
  • Author(s): Nobuaki Takahashi, Sayaka Hamada-Nakahara, Yuzuru Itoh, Kazuhiro Takemura, Atsushi Shimada,Yoshifumi Ueda, Manabu Kitamata, Rei Matsuoka, Kyoko Hanawa-Suetsugu, Yosuke Senju, Masayuki X. Mori, Shigeki Kiyonaka, Daisuke Kohda, Akio Kitao, Yasuo Mori and Shiro Suetsugu
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 4994-4994
  • DOI: 10.1038/ncomms5994
  • NAID: 130005100825
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ligand-Induced Protein Responses and Mechanical Signal Propagation Described by Linear Response Theories (2014)
  • Author(s): Lee-Wei Yang, Akio Kitao, Bang-chieh Huang and Nobuhiro Go
  • Journal Title: Biophysical Journal Volume: 107 Issue: 6 Pages: 1415-1425
  • DOI: 10.1016/j.bpj.2014.07.049
  • Peer Reviewed
• [Journal Article] Molecular Simulation Methods to Enhance Soft Protein Motions (2014)
  • Author(s): 原田隆平,北尾彰朗
  • Journal Title: Seibutsu Butsuri Volume: 54 Issue: 3 Pages: 167-171
  • DOI: 10.2142/biophys.54.167
  • NAID: 130004719369
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed / Open Access
• [Journal Article] カスケード型超並列シミュレーションによるタンパク質構造遷移のパスウェイ探索 (2014)
  • Author(s): 西原泰孝, 原田隆平, 北尾彰朗
  • Journal Title: 統計数理 Volume: 62 Pages: 273-284
  • NAID: 120006020818
  • Peer Reviewed
• [Journal Article] Conformational transition pathway and free energy analyses of proteins by parallel cascade selection molecular dynamics (PaCS-MD) (2014)
  • Author(s): Ryuhei Harada, Yasutaka Nishihara, Nobuhiko Wakai, and Akio Kitao
  • Journal Title: AIP Conference Proceedings Volume: 1618 Pages: 86-86
  • DOI: 10.1063/1.4897682
  • Peer Reviewed / Open Access
• [Journal Article] Mechanism of Deep-sea Fish α-Actin Pressure Tolerance Investigated by Molecular Dynamics Simulations (2014)
  • Author(s): Nobuyuki Wakai and Akio Kitao
  • Journal Title: PLoS ONE Volume: 9 Issue: 1 Pages: e85852-e85852
  • DOI: 10.1371/journal.pone.0085852
  • Peer Reviewed
• [Journal Article] CyClus: A fast, comprehensive cylindrical interface approximation clustering/reranking method for rigid-body protein-protein docking decoys (2013)
  • Author(s): Satoshi Omori and Akio Kitao
  • Journal Title: Proteins Volume: 81 Issue: 6 Pages: 1005-1016
  • DOI: 10.1002/prot.24252
  • Peer Reviewed
• [Journal Article] Inhibition of a type III secretion system by the deletion of a short loop in one of its membrane proteins (2013)
  • Author(s): Vladimir A. Meshcheryakov, Akio Kitao, Hideyuki Matsunami and Fadel A. Samatey
  • Journal Title: Acta Crystallographica Section D-Biological Crystallography Volume: D69 Issue: 5 Pages: 812-820
  • DOI: 10.1107/s0907444913002102
  • Peer Reviewed
• [Journal Article] Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway (2013)
  • Author(s): Ryuhei Harada and Akio Kitao
  • Journal Title: Journal of Chemical Physics Volume: 139 Issue: 3
  • DOI: 10.1063/1.4813023
  • Peer Reviewed
• [Journal Article] MuSTAR MD: Multi-scale sampling using temperature accelerated and replica exchange molecular dynamics (2013)
  • Author(s): Yu Yamamori and Akio Kitao
  • Journal Title: Journal of Chemical Physics Volume: 139 Issue: 14
  • DOI: 10.1063/1.4823743
  • Peer Reviewed
• [Journal Article] 分子シミュレーションによるタンパク質ダイナミクスとテラヘルツ分光 (2013)
  • Author(s): 城地保昌,北尾彰朗
  • Journal Title: 化学工業 Volume: 64 Pages: 7-13
• [Journal Article] Free-energy analysis of lysozyme-triNAG binding modes with all-atom molecular dynamics simulation combined with the solution theory in the energy representation (2013)
  • Author(s): K. Takemura, R. R. Burri, T. Ishikawa, T. Ishikura, S. Sakuraba, N. Matubayasi, K. Kuwata, and A. Kitao
  • Journal Title: Chem. Phys. Lett Volume: 559 Pages: 94-98
  • DOI: 10.1016/j.cplett.2012.12.063
  • Peer Reviewed
• [Journal Article] A theoretical study of the two binding modes between lysozyme and tri-NAG with an explicit solvent model based on the fragment molecular orbital method (2013)
  • Author(s): T. Ishikawa, R. R. Burri, Y. O. Kamatari, S. Sakuraba, N. Matubayasi, A. Kitao, and K. Kuwata
  • Journal Title: Phys. Chem. Chem. Phys Volume: 15 Issue: 10 Pages: 3646-3654
  • DOI: 10.1039/c3cp42761g
  • Peer Reviewed
• [Journal Article] Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation (2012)
  • Author(s): K. Takemura, H. Guo, S. Sakuraba, N. Matubayasi, and A. Kitao
  • Journal Title: J. Chem. Phys Volume: 137 Issue: 21
  • DOI: 10.1063/1.4768901
  • Peer Reviewed
• [Journal Article] Water model tuning for improved reproduction of rotational diffusion and NMR spectral density (2012)
  • Author(s): Kazuhiro Takemura and Akio Kitao
  • Journal Title: J. Phys. Chem. B Volume: 116 Issue: 22 Pages: 6279-6287
  • DOI: 10.1021/jp301100g
  • Peer Reviewed
• [Journal Article] The fast-folding mechanism of villin headpiece subdomain studied by multi-scale distributed computing (2012)
  • Author(s): Ryuhei Harada, Akio Kitao
  • Journal Title: Journal of Chemical Theory and Computation Volume: 8(1) Issue: 1 Pages: 290-299
  • DOI: 10.1021/ct200363h
  • Peer Reviewed
• [Journal Article] Exploring the Folding Free Energy Landscape of a β-Hairpin Miniprotein, Chignolin, Using Multiscale Free Energy Landscape Calculation Method (2011)
  • Author(s): Ryuhei Harada, Akio Kitao
  • Journal Title: The Journal of Physical Chemistry B Volume: 115(27) Issue: 27 Pages: 8806-8812
  • DOI: 10.1021/jp2008623
  • Peer Reviewed
• [Journal Article] Transform and relax sampling for highly anisotropic systems : Application to protein domain motion and folding (2011)
  • Author(s): Akio Kitao
  • Journal Title: The Journal of Chemical Physics Volume: 135(4) Issue: 4 Pages: 45101-45114
  • DOI: 10.1063/1.3613676
  • Peer Reviewed
• [Journal Article] Screw motion regulates multiple functions of T4 phage protein gene product 5 during cell puncturing (2011)
  • Author(s): Nishima W, Kanamaru S, Arisaka F, Kitao A
  • Journal Title: J Am Chem Soc Volume: 133(34) Issue: 34 Pages: 13571-13576
  • DOI: 10.1021/ja204451g
  • Peer Reviewed
• [Presentation] Membrane deformation induced by proteins (2015)
  • Author(s): Akio Kitao
  • Organizer: 分子研研究会「生体分子の構造、ダイナッミクス、機能」「Architecture, dynamics, and functionality of molecular biosystems」
  • Place of Presentation: 自然科学研究機構 分子研 研究棟201セミナー室（愛知県・岡崎市）
  • Year and Date: 2015-03-30 – 2015-03-31
  • Invited
• [Presentation] 高度な分子動力学によるタンパク質の機能シミュレーション (2015)
  • Author(s): 北尾彰朗
  • Organizer: スーパーコンピュータワークショップ２０１５
  • Place of Presentation: 岡崎コンファレンスセンター（愛知県・岡崎市）
  • Year and Date: 2015-01-29 – 2015-01-30
  • Invited
• [Presentation] Observing soft functional motion of proteins in silico (2014)
  • Author(s): Akio Kitao
  • Organizer: 第52回日本生物物理学会年会シンポジウム
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] Molecular simulation of proteins: Pressure tolerance of deep-sea fish actin and membrane deformation induced by I-BAR domain (2014)
  • Author(s): Akio Kitao
  • Organizer: 1st SPIRITS Workshop“Manipulation of Integrated Molecular Reaction Processes in living cell
  • Place of Presentation: Kyoto/Campus Plaza Kyoto
  • Year and Date: 2014-09-02
  • Invited
• [Presentation] Conformational Transition Pathway and Free Energy Analyses of Proteins by Parallel Cascade Selection Molecular Dynamics (PaCS-MD) (2014)
  • Author(s): Ryuhei Harada, Yasutaka Nishihara, Nobuhiko Wakai and Akio Kitao
  • Organizer: International Conference of Computational Methods in Sciences and Engineering (ICCMSE 2014)
  • Place of Presentation: Athens, Greece/Metropolitan Hotel
  • Year and Date: 2014-04-04 – 2014-04-07
  • Invited
• [Presentation] バイオ分子が働く様子をコンピュータでみてみよう (2014)
  • Author(s): 北尾彰朗
  • Organizer: 化学への招待－講演会；コンピュータ化学で物質の振舞いや生命現象を「見る」
  • Place of Presentation: 東京都目黒区/東大生産技術研究所コンベンションホール
  • Invited
• [Presentation] 柔らかさを利用したタンパク質とその集合体の機能制御 (2014)
  • Author(s): 北尾彰朗
  • Organizer: 日本化学会 第94春季年会 シンポジウム
  • Place of Presentation: 愛知県名古屋市/名古屋大学東山キャンパス
  • Invited
• [Presentation] 蛋白質構造ダイナミクスと機能の関係を探るより効率的な分子シミュレーション (2013)
  • Author(s): 北尾彰朗
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: 鳥取県鳥取市/とりぎん文化会館
  • Invited
• [Presentation] How Can Soft Molecular Machinery Be Well-Regulated? Structure and Function of Bacterial Flagella (2013)
  • Author(s): Akio Kitao
  • Organizer: 第15回日韓分子科学シンポジウム
  • Place of Presentation: 兵庫県神戸市/ホテル北野プラザ六甲荘
  • Invited
• [Presentation] 分子シミュレーションによる大腸菌べん毛モーター固定子MotA/Bの立体構造モデリングとプロトン透過メカニズム (2013)
  • Author(s): 北尾彰朗
  • Organizer: 第3回分子モーター討論会
  • Place of Presentation: 東京都文京区/東京大学フードサイエンス棟中島董一郎記念ホール
  • Invited
• [Presentation] Exploring protein conformational transition pathways with efficient molecular simulation method (2013)
  • Author(s): Akio Kitao
  • Organizer: Telluride Science Research Center Protein Dynamics Workshop on Protein Dynamics
  • Place of Presentation: Telluride, CO, USA
  • Invited
• [Presentation] 集団座標による分子シミュレーションの解析 (2013)
  • Author(s): 北尾彰朗
  • Organizer: 第7回分子シミュレーションスクール」「TCCIウィンターカレッジ」
  • Place of Presentation: 愛知県岡崎市/岡崎コンファレンスセンター
  • Invited
• [Presentation] 巨大生体超分子の構造転移制御メカニズム (2013)
  • Author(s): 北尾彰朗
  • Organizer: HPCI戦略プログラム 分野1×分野2 シンポジウムin 名大「生体分子複合システムを計算する－相互作用は何をもたらすのか－」
  • Place of Presentation: 愛知県名古屋市/名古屋大学IB電子情報館
  • Invited
• [Presentation] Structure modeling of the stator in bacterial flagellar motor and implication for selective permeation mechanism of proton (2013)
  • Author(s): 北尾彰朗
  • Organizer: JSPS二国間交流事業 第4回日仏セミナー『細胞内の時間・空間階層構造のイメージング－分子から細胞に至るダイナミクス俯瞰－』
  • Place of Presentation: Spring8 及びSACLA （兵庫県）
  • Invited
• [Presentation] 細菌べん毛モーター固定子複合体MotA/Bへのイオン透過機構 (2013)
  • Author(s): 西原泰孝，北尾彰朗
  • Organizer: 2012年度べん毛交流会
  • Place of Presentation: 喜びの宿しん喜 （群馬県）
• [Presentation] 水とタンパク質の構造揺らぎの理論解析 (2012)
  • Author(s): 北尾彰朗
  • Organizer: 新学術合同交際シンポジウム「ゆらぎと水―生命のエネルギーと機能の分子機構を探る」
  • Place of Presentation: 大阪ガーデンパレス （大阪府）
  • Invited
• [Presentation] 細菌べん毛モーター固定子複合体MotA/B チャネルの選択的透過メカニズム (2012)
  • Author(s): 西原泰孝，北尾彰朗
  • Organizer: 第50回日本生物物理学会年会
  • Place of Presentation: 名古屋大学東山キャンパス （愛知県）
• [Presentation] Multi-scale modeling of protein complex structures (2012)
  • Author(s): Akio Kitao
  • Organizer: Mini-Symposium on Modeling, Simulation and Function of Biomolecular Assemblies
  • Place of Presentation: 東京大学伊藤国際学術センター （東京都）
• [Presentation] 細菌べん毛モーター固定子複合体MotA/Bチャネルの選択的透過メカニズム (2012)
  • Author(s): 西原泰孝，北尾彰朗
  • Organizer: 第12回東京大学生命科学シンポジウム
  • Place of Presentation: 東京大学山上会館 （東京都）
• [Presentation] Finding Function-relevant Dynamics in Proteins (2012)
  • Author(s): 北尾彰朗
  • 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 （奈良県）
  • Invited
• [Presentation] タンパク質ソフトモードのサンプリングと相関解析 (2012)
  • Author(s): 北尾彰朗
  • Organizer: 研究会「高次元のサンプリングとデータ解析からみたシミュレーション科学」
  • Place of Presentation: 統計数理研究所 （東京都）
  • Invited
• [Presentation] Enhancement of soft protein dynamics and efficient (2011)
  • Author(s): Akio Kitao
  • Organizer: Telluride Science Research Center Workshop
  • Place of Presentation: Telluride (USA)
  • Invited
• [Presentation] 機能を生み出すタンパク質の異方的ダイナミクス (2011)
  • Author(s): 北尾彰朗
  • Organizer: 日本物理学会2011年秋季大会
  • Place of Presentation: 富山大学五福キャンパス (富山県）
  • Invited
• [Presentation] 分子シミュレーションによるタンパク質ダイナミクスとテラヘルツ分光 (2011)
  • Author(s): 北尾彰朗
  • Organizer: 日本分光学会 テラヘルツ分光部会 シンポジウム テラヘルツ分光法の最先端V ～バイオテラヘルツ分光～
  • Place of Presentation: パシフィコ横浜 （神奈川県）
  • Invited
• [Presentation] 生体超分子の構造変化を制御する分子メカニズム (2011)
  • Author(s): 北尾彰朗
  • Organizer: 分子研研究会「実験と理論による高次分子システムの機能発現の分子論的理解」
  • Place of Presentation: 岡崎コンファレンスセンター （愛知県）
  • Invited
• [Remarks] 東京大学分子細胞生物学研究所計算分子機能研究分野
  • URL: http://www.iam.u-tokyo.ac.jp/MolDes/
• [Remarks] 東京大学分子細胞生物学研究所計算分子機能研究分野
  • URL: http://www.iam.u-tokyo.ac.jp/MolDes/
• [Remarks] 東京大学分子細胞生物学研究所計算分子機能研究分野
  • URL: http://www.iam.u-tokyo.ac.jp/MolDes/