柔らかいタンパク質・DNA分子認識のマルチスケール計算研究

• Project Area: Science on Function of Soft Molecular Systems by Cooperation of Theory and Experiment
• Project/Area Number: 26104517
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Kyoto University
• Principal Investigator: 高田 彰二 京都大学, 理学(系)研究科(研究院), 教授 (60304086)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 柔らかい / DNA / 分子認識 / マルチスケール / シミュレーション

Outline of Annual Research Achievements

概要：蛋白質のDNA結合によってDNAは曲がり、曲がったDNAは蛋白質の動態に影響することが示唆されてきた。本研究では、蛋白質結合とDNA変形の動的な相互依存関係について、細菌蛋白質HUを例にとって、マルチスケール分子シミュレーションによって理論解析を行い、高い時空間分解能で、蛋白質結合とDNA変形の動態を解析することに成功した。
１．はじめに：蛋白質のDNA結合によってDNAは曲がり、曲がったDNAは逆に蛋白質の動態に影響する。その共役関係を詳細に調べるのが本研究の目的である。
２．研究成果・進捗状況：２－１．蛋白質のDNA結合、DNA上のスライディング、DNAの屈曲の動的関連性まず分子シミュレーションの結果は、HUがAT塩基をやや好むこと、ギャップなどにより折れ曲がったDNAに強く結合するという実験的に知られている結果をよく再現した。HUは、DNAの屈曲した部分に結合すると、DNAとの結合表面積を増やすことでより強固な複合体となる。さらに、動的にみてHUの結合とDNAの折れ曲がりは強く共役していることが分かった。興味深いことに、HUは、自身の結合によってDNAが強く曲がったときには拡散を一時的にストップし、その後DNAの曲がりが戻ると拡散を再開することがわかった。蛋白質の結合によって有機されたDNAの曲がりの動的な変動が、そこに結合する蛋白質の動態に影響する。ほかの14個のDNA結合蛋白質についても同様の解析を行い、その動態を比較した。
２－２．p53の特異的DNA配列の認識機構の研究：2本鎖DNA上にその特異配列が含まれるとき、p53の4量体が検索し、その配列を認識する様子をシミュレーションし、その動態を解析した。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations (2015)
  • Author(s): Shoji Takada, Ryo Kanada, Cheng Tan, Tsuyoshi Terakawa, Wenfei Li, and Hiroo Kenzaki
  • Journal Title: Accounts of Chemical Research Volume: 48 Issue: 12 Pages: 3026-3035
  • DOI: 10.1021/acs.accounts.5b00338
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] p53 dynamics upon response element recognition explored by molecular simulations (2015)
  • Author(s): Tsuyoshi Terakawa and Shoji Takada
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 17107-17107
  • DOI: 10.1038/srep17107
  • NAID: 120005758220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Partial Unwrapping and Histone Tail Dynamics in Nucleosome Revealed by Coarse-Grained Molecular Simulations (2015)
  • Author(s): Hiroo Kenzaki and Shoji Takada
  • Journal Title: PLoS Computational Biology Volume: 11 Issue: 8 Pages: e1004443-e1004443
  • DOI: 10.1371/journal.pcbi.1004443
  • NAID: 120005947019
  • Peer Reviewed / Open Access
• [Journal Article] How Co-translational Folding of Multi-domain Protein Is Affected by Elongation Schedule: Molecular Simulations (2015)
  • Author(s): Tomohiro Tanaka, Naoto Hori, and Shoji Takada
  • Journal Title: PLoS Computational Biology Volume: 11 Issue: 7 Pages: e1004356-e1004356
  • DOI: 10.1371/journal.pcbi.1004356
  • NAID: 120005946993
  • Peer Reviewed / Open Access
• [Journal Article] On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases (2015)
  • Author(s): Alexander Krah and Shoji Takada
  • Journal Title: Biochimica et Biophysica Acta - Bioenergetics Volume: 1847 Issue: 10 Pages: 1101-1112
  • DOI: 10.1016/j.bbabio.2015.05.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Couplings between Hierarchical Conformational Dynamics from Multi-Time Correlation Functions and Two-Dimensional Lifetime Spectra: Application to Adenylate Kinase (2015)
  • Author(s): J. Ono, S. Takada, and S. Saito
  • Journal Title: Journal of Chemical Physics Volume: 142 Issue: 21 Pages: 212404-212404
  • DOI: 10.1063/1.4914328
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dimer domain swapping versus monomer folding in apo-myoglobin studied by molecular simulations (2015)
  • Author(s): Koji Ono, Mashiho Ito, Shun Hirotab and Shoji Takada
  • Journal Title: Phys. Chem. Chem. Phys. Volume: 17 Issue: 7 Pages: 5006-5013
  • DOI: 10.1039/c4cp05203j
  • Peer Reviewed
• [Journal Article] Energy landscape views for interplays among folding, binding, and allostery of calmodulin domain (2015)
  • Author(s): Wenfei Li, Wei Wang, and Shoji Takada,
  • Journal Title: Proceedings of the National Academy of Sciences USA Volume: 111(29) Issue: 29 Pages: 10550-10555
  • DOI: 10.1073/pnas.1402768111
  • Peer Reviewed
• [Journal Article] RESPAC : Method to Determine Partial Charges in Coarse-greined Prote in Model and Its Application to DNA-Binding Proteins' Journal of Chemical Theory and Computation (2014)
  • Author(s): Tsuyoshi Terakawa and Shoji Takadae
  • Journal Title: Journal of Chemical Theory and Computation Volume: 10 Issue: 2 Pages: 711-721
  • DOI: 10.1021/ct4007162
  • Peer Reviewed
• [Presentation] Flexibility in protein-DNA interactions studied by molecular simulations (2015)
  • Author(s): Shoji Takada
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 金沢大学角間キャンパス（金沢市）
  • Year and Date: 2015-09-13
• [Presentation] Heterochromatin protein 1 binding to nucleosomes studied by coarse-grained simulations (2015)
  • Author(s): Shuhei Watanabe, Yuichi Mishima, Isao Suetake and Shoji Takada
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 金沢大学角間キャンパス（金沢市）
  • Year and Date: 2015-09-13
• [Presentation] IDP in protein-DNA interactions studied by coarse-grained simulations (2015)
  • Author(s): Shoji Takada
  • Organizer: The CECAM workshop on “Intrinsically Disordered Proteins – Bringing together Physics, Computation, and Biology”
  • Place of Presentation: Zurich, Switzerland
  • Year and Date: 2015-08-18
  • Int'l Joint Research / Invited
• [Presentation] Flexibility in protein-DNA molecular recognition studied by multiscale simulations (2015)
  • Author(s): Shoji Takada
  • Organizer: 「柔らかな分子系」国際シンポジウム（第3回公開シンポジウム）
  • Place of Presentation: 日本科学未来館（東京）
  • Year and Date: 2015-07-09
• [Presentation] Protein-DNA Complexes in crowded chromatin-like environment (2015)
  • Author(s): Shoji Takada
  • Organizer: IPR Seminar on Molecular Crowding and Macromolecular Association
  • Place of Presentation: Institute for Protein Research, Osaka University
  • Year and Date: 2015-02-05
  • Invited
• [Presentation] Transition path time over the barrier in protein folding (2014)
  • Author(s): Shoji Takada
  • Organizer: Indo-Japan Joint Workshop on “Frontiers in Molecular Spectroscopy: Fundamentals and Applications to Material and Biology”
  • Place of Presentation: Nara Prefectural New Public Hall
  • Year and Date: 2014-11-25 – 2014-11-28
  • Invited
• [Presentation] On free energy landscape and "transition path" in folding of Go model (2014)
  • Author(s): Shoji Takada
  • Organizer: International Workshop “Over the Barriers of Transition Paths: Dynamical Processes in Proteins and Complex Molecular Systems”
  • Place of Presentation: Tokyo Institute of Technology
  • Year and Date: 2014-06-28
  • Invited
• [Presentation] Coarse-Grained Modeling of Protein-DNA complexes (2014)
  • Author(s): Shoji Takada
  • Organizer: Workshop on "Coarse-graining as a Frontier of Statistical Mechanics"
  • Place of Presentation: Santa Fe, USA
  • Year and Date: 2014-06-16 – 2014-06-18
  • Invited
• [Presentation] ATP Hydrolysis Mechanism in Kinesin Studied by Combined QM/MM Meta-dynamics Simulations (2014)
  • Author(s): Tokyo ATPase workshop
  • Organizer: Tokyo ATPase workshop
  • Place of Presentation: Tokyo Takeda Bldg. Takeda Hall The University of Tokyo
  • Year and Date: 2014-06-02 – 2014-06-03
  • Invited
• [Book] 生物物理55(1)：計算科学と実験科学の組み合わせにより明らかになった 多剤排出トランスポーターAcrBの分子メカニズム (2015)
  • Author(s): 村上聡、山根努、池口満徳、高田彰二
  • Publisher: 日本生物物理学会
• [Book] 粗視化シミュレーションと実験科学, 1分子ナノバイオ計測 (2014)
  • Author(s): 高田彰二、野地博幸 編
  • Publisher: 化学同人