立体構造情報に基づいた網羅的タンパク質間相互作用予測システムの開発

• Project/Area Number: 11J08750
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Bioinformatics/Life informatics
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: 大上 雅史 東京工業大学, 大学院情報理工学研究科, 特別研究員(DC1)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥1,900,000 (Direct Cost: ¥1,900,000); Fiscal Year 2013: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2012: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2011: ¥700,000 (Direct Cost: ¥700,000)
• Keywords: バイオインフォマティクス / タンパク質間相互作用予測 / タンパク質ドッキング / アポトーシス / ハイパフォーマンスコンピューティング / タンパク質立体構造 / バイオインフォティクス / タンパク質間相互作用 / 構造アンサンブル / タンパク質-RNA間相互作用

Research Abstract

タンパク質の生体内相互作用ネットワークは, 病因の理解や創薬ターゲット決定に重要であるが, 大規模ネットワークを実験的に導くことは多大なコストを要するため, 計算機によって大規模なネットワークを予測する技術が求められている. 本研究は公共データベースに登録されたタンパク質の立体構造情報を利用して, 複合体形成を擬似的に行うタンパク質ドッキング計算によってタンパク質の相互作用の有無を高速に予測することを目標としており, 本年度は提案した新規手法の大規模並列実装や, GPUアクセラレータ上での実装による大幅な高速化を行った. 「京」やTSUBAMEといった超並列計算機を効率的に利用するための, MPIとOpenMPライブラリを併用したハイブリッド並列化や, タンパク質の前処理や回転計算をGPU上で計算させることでCPU-GPU間のデータ転送コストの削減などを行い, 東工大TSUBAME2.5システム400ノードの計算機環境において, 100万件規模のタンパク質間相互作用予測計算をおよそ1日で完了できるようになった.
さらに, 当該予測システムは単体の複合体構造情報のみを用いるものであるが, 既存の複合体構造情報を併用することで精度, 特に選択度を向上させることのできる手法を提案した. これらはヒトアポトーシスパスウェイ中のタンパク質群(57種)に適用し, 未知の相互作用の検出を試みた. 提案手法によって検出された未知の相互作用の例としてカスパーゼ-3とカスパーゼ-7という2つのタンパク質の相互作用を挙げ, 予測された複合体構造などに基づいて検証を行った.

Strategy for Future Research Activity

(抄録なし)

Research Products

• [Journal Article] MEGADOCK : An all-to-all protein-protein interaction prediction system using tertiary structure data (2014)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Journal Title: Protein and Peptide Letters Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Protein-protein interaction network prediction by using rigid-body docking tools : apphcation to bacterial chemotaxis (2014)
  • Author(s): Yuri Matsuzaki, Masahito Ohue, Nobuyuki Uchikoga, Yutaka Akiyama
  • Journal Title: Protein and Peptide Letters Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Re-docking scheme for generating near-native protein complexes by assembling residue interaction fingerprints (2013)
  • Author(s): Nobuyuki Uchikoga, Yuri Matsuzaki, Masahito Ohue, Takatsugu Hirokawa, Yutaka Akiyama
  • Journal Title: PLOS ONE Volume: 8 Issue: 7 Pages: e69365-e69365
  • DOI: 10.1371/journal.pone.0069365
  • Peer Reviewed
• [Journal Article] 配列情報に基づくタンパク質間相互作用予測の構造情報付加による高精度化 (2013)
  • Author(s): 中嶋悠介, 大上雅史, 越野亮
  • Journal Title: FIT2013 第12回情報科学技術フォーラム講演論文集 Volume: 第二分冊 Pages: 63-68
  • Peer Reviewed
• [Journal Article] MEGADOCK 3.0 : A high-performance protein-protein interaction prediction software using hybrid parallel computing for petascale supercomputing emvironmnts (2013)
  • Author(s): Yuri Matsuzaki, Nobuyuki Uchikoga, Masahito Ohue, Takehiro Shimoda, Tbshiyuki Sato, Takashi Ishida, Yutaka Akiyama
  • Journal Title: Source Code for Biology and Medicine Volume: 8 Issue: 1 Pages: 18-18
  • DOI: 10.1186/1751-0473-8-18
  • Peer Reviewed
• [Journal Article] Highly Precise Protein-Protein Interaction Prediction Based on Consens us Between Template-Based and de Novo Docking Methods (2013)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Takehiro Shimoda, Takashi Ishida, Yutaka Akiyama
  • Journal Title: BMC Proceedings Volume: 7 Issue: S7
  • DOI: 10.1186/1753-6561-7-s7-s6
  • Peer Reviewed
• [Journal Article] MEGADOCK-GPU : Acceleration of Protein-Protein Docking Calculation on GPUs (2013)
  • Author(s): Takehiro Shimoda, Takashi lshida, Shuji Suzuki, Masahito Ohue, Yutaka Akiyama
  • Journal Title: Proceedings of the ACM Conference on Bioinformatics, Computational Biology and Biomedicine 2013 (ACM-BCB 2013) Pages: 884-890
  • DOI: 10.1145/2506583.2506693
  • Peer Reviewed
• [Journal Article] Improvement of the Protein-Protein Docking Prediction by Introducing a Simple Hydrophobic Interaction Model: an Application to Interaction Pathway Analysis, (2012)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Takashi Ishida, Yutaka Akiyama
  • Journal Title: Lecture Notes in Computer Science Volume: 7632 Pages: 178-187
  • DOI: 10.1007/978-3-642-34123-6_16
  • ISBN: 9783642341229, 9783642341236
  • Peer Reviewed
• [Journal Article] Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology (2011)
  • Author(s): Fleishman SJ, 他(研究代表者含む,全96人)
  • Journal Title: Journal of Molecular Biology Volume: 414 Issue: 2 Pages: 289-302
  • DOI: 10.1016/j.jmb.2011.09.031
  • Peer Reviewed
• [Journal Article] Docking-calculation-based Method for Predicting Protein-RNA Interactions (2011)
  • Author(s): Ohue M, Matsuzaki Y, Akiyama Y
  • Journal Title: Genome Informatics Volume: 25 Pages: 25-39
  • Peer Reviewed
• [Presentation] MEGADOCK 4.0 : mega-dock per dayへの道のり (2014)
  • Author(s): 大上雅史, 下田雄大, 松崎由理, 内古閑伸之, 鈴木脩司, 石田貴士, 秋山泰
  • Organizer: 生命情報科学若手の会 第5回研究会
  • Place of Presentation: 東京大学検見川セミナーハウス(千葉県)
  • Year and Date: 2014-02-17
• [Presentation] Highly precise protein-protein interaction prediction by integrating template-based and template-free protein docking (2013)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Takehiro Shimoda, Takashi Ishida, Yutaka Akiyama
  • Organizer: The 2013 Annual Conference of the Japanese Society for Bioinformatics (JSBi2013)
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2013-10-29
• [Presentation] Structure based protein-protein interaction network prediction of EGFR signaling related proteins using MEGADOCK (2013)
  • Author(s): Yuri Matsuzaki, Masahito Ohue, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: 2nd IIT Madras - Tokyo Tech Joint Symposium on Techniques and Applications of Bioinformatics
  • Place of Presentation: インド, チェンナイ
  • Year and Date: 2013-09-27
• [Presentation] Re-docking scheme of protein-protein interactions for generating near-native interaction patterns in difficult docking cases (2013)
  • Author(s): Nobuyuki Uchikoga, Yuri Matsuzaki, Masahito Ohue, Takatsugu Hirokawa, Yutaka Akiyama
  • Organizer: 2nd IIT Madras - Tokyo Tech Joint Symposium on Techniques and Applications of Bioinformatics
  • Place of Presentation: インド, チェンナイ
  • Year and Date: 2013-09-27
• [Presentation] The MEGADOCK project : Ultra-high-performance protein-protein interaction prediction tools on supercomputing environments (2013)
  • Author(s): Takehiro Shimoda, Masahito Ohue, Yuri Matsuzaki, Takayuki Fujiwara, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: ACM Conference on Bioinformatics, Computatioal Biology and Biomedical Informatics (ACM-BCB2013)
  • Place of Presentation: 米国, ベセスダ
  • Year and Date: 2013-09-23
• [Presentation] Improvement of protein-protein interaction prediction by integrating template-based and template-free protein docking (2013)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Takehiro Shimoda, Takashi Ishida, Yutaka Akiyama
  • Organizer: ACM Conference on Bioinformatics, Computatioal Biology and Biomedical Informatics (ACM-BCB2013)
  • Place of Presentation: 米国, ベセスダ
  • Year and Date: 2013-09-23
• [Presentation] Highly Precise Protein-Protein Interaction Prediction Based on Consensus Between Template-Based and de Novo Docking Methods (2013)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Takehiro Shimoda, Takashi Ishida, Yutaka Akiyama
  • Organizer: Great Lakes Bioinformatics Conference 2013 (GLBIO2013)
  • Place of Presentation: 米国, ピッツバーグ
  • Year and Date: 2013-05-15
• [Presentation] Protein-protein interaction prediction based on rigid-body docking with ultra-high-performance computing technique : applications to affinity prediction on CAPRI round 21 and interactome analyses (2013)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Nobuyuki Uchikoga, Kohei Yamamoto, Takayuki Fujiwara, Takehiro Shimoda, Toshiyuki Sato, Takashi Ishida, Yutaka Akiyama
  • Organizer: CAPRI 2013 5th Evaluation Meeting
  • Place of Presentation: オランダ, ユトレヒト
  • Year and Date: 2013-04-17
• [Presentation] MEGADOCK 3.0 : 超並列タンパク質間相互作用予測システム (2013)
  • Author(s): 大上雅史, 松崎由理, 内古閑伸之, 山本航平, 下田雄大, 藤原隆之, 石田貴士, 秋山泰
  • Organizer: 生命情報科学若手の会4回研究会
  • Place of Presentation: 基礎生物学研究所, 岡崎市, 愛知県
  • Year and Date: 2013-03-01
• [Presentation] MEGADOCK : 大規模タンパク質間相互作用予測システムとその応用 (2013)
  • Author(s): 大上雅史, 松崎由理, 石田貴士, 秋山泰
  • Organizer: 2013年ハイパフォーマンスコンピューティングと計算科学シンポジウム(HPCS2013)
  • Place of Presentation: 東京工業大学大岡山キャンパス, 東京都
  • Year and Date: 2013-01-15
• [Presentation] MEGADOCK : a High-speed Protein-protein Interaction Prediction System by All-to-all Physical Docking (2012)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: ISCB-Asia/SCCG 2012
  • Place of Presentation: 深セン, 中国
  • Year and Date: 2012-12-17
• [Presentation] Application of exhaustive protein-protein interaction prediction system by using protein docking to signal transduction pathways (2012)
  • Author(s): Yuri Matsuzaki, Masahito Ohue, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: ISCB-Asia/SCCG 2012
  • Place of Presentation: 深セン, 中国
  • Year and Date: 2012-12-17
• [Presentation] MEGADOCKを用いたタンパク質間相互作用予測のヒトアポトーシスパスウェイ解析への応用 (2012)
  • Author(s): 大上雅史, 松崎由理, 石田貴士, 秋山泰
  • Organizer: 情報処理学会第32回バイオ情報学研究会
  • Place of Presentation: 京都大学桂キャンパス, 京都府
  • Year and Date: 2012-12-06
• [Presentation] 構造情報に基づくタンパク質間相互作用ネットワーク予測精度の改善 (2012)
  • Author(s): 山本航平, 大上雅史, 石田貴士, 秋山泰
  • Organizer: 情報処理学会第32回バイオ情報学研究会
  • Place of Presentation: 京都大学桂キャンパス, 京都
  • Year and Date: 2012-12-06
• [Presentation] Improvement of the Protein-Protein Docking Prediction by Introducing a Simple Hydrophobic Interaction Model : an Application to Interaction Pathway Analysis (2012)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Takashi Ishida, Yutaka Akiyama
  • Organizer: The 7th IAPR International Conference on Pattern Recognition in Bioinformatics (PRIB2012)
  • Place of Presentation: 東京工業大学大岡山キャンパス, 東京都
  • Year and Date: 2012-11-08
• [Presentation] MEGADOCK : A rapid screening system of protein-protein interactions with all-to-all physical docking (2012)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: 20th Annual International Conference Oil Intelligent Systems for Molecular Biology (ISMB2012)
  • Place of Presentation: ロングビーチ, カリフォルニア州, アメリカ
  • Year and Date: 2012-07-19
• [Presentation] Application of exhaustive protein-protein interaction prediction system by using protein docking to signal transduction pathways (2012)
  • Author(s): Yuri Matsuzaki, Masahito Ohue, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: 20th Annual International Conference on Intelligent Systems for Molecular Biology (ISMB2012)
  • Place of Presentation: ロングビーチ, カリフォルニア州, アメリカ
  • Year and Date: 2012-07-19
• [Presentation] MEGADOCK : A Rapid Screening System of Protein-Protein Interactions by Exhaustive Docking (2012)
  • Author(s): Masahito Ohue, Yuri Matsuzaki, Nobuyuki Uchikoga, Takashi Ishida, Yutaka Akiyama
  • Organizer: 3DSIG : The 8th structural bioinformatics and computational biophysics meeting
  • Place of Presentation: ロングビーチ, カリフォルニア州, アメリカ
  • Year and Date: 2012-07-17
• [Presentation] Application of Exhaustive Protein- Protein Interaction Prediction System by Using Protein Docking to Signal Transduction Pathways (2012)
  • Author(s): Yuri Matsuzaki, Nobuyuki Uchikoga, Masahito Ohue, Yutaka Akiyama
  • Organizer: 3DSIG : The 8th structural bioinformatics and computational biophysics meeting
  • Place of Presentation: ロングビーチ, カリフォルニア州, アメリカ
  • Year and Date: 2012-07-17
• [Presentation] 簡易疎水性相互作用モデルによるタンパク質間ドッキング予測の高制度化 (2012)
  • Author(s): 大上雅史, 石田貴士, 秋山泰
  • Organizer: 情報処理学会第29回バイオ情報学研究会
  • Place of Presentation: 琉球大学, 沖縄県
  • Year and Date: 2012-06-29
• [Presentation] Protein Complex Structure Prediction with Normal Mode Ensemble and Physical Docking (2012)
  • Author(s): Ohue M, Matsuzaki Y, Uchikoga N, Ishida T, Akiyama Y
  • Organizer: Bioinformatics week in Odaiba 2011
  • Place of Presentation: 産総研臨海副都心センター,東京都
  • Year and Date: 2012-01-24
• [Presentation] Bound state structure estimation of protein-protein complex using rigid-body protein-protein docking method (2012)
  • Author(s): Ohue M, Matsuzaki Y, Uchikoga N, Ishida T, Akiyama Y
  • Organizer: The 10th Asia-Pacific Bioinformatics Conference
  • Place of Presentation: リッジズホテル,メルボルン,オーストラリア
  • Year and Date: 2012-01-18
• [Presentation] Binding Conformation Prediction of a Protein Complex Using Physical Docking (2011)
  • Author(s): Ohue M, Matsuzaki Y, Uchikoga N, Ishida T, Akiyama Y
  • Organizer: GCOE Compview Final Symposium (Preliminary event of ISAAC 2011)
  • Place of Presentation: ワークピア横浜,神奈川県
  • Year and Date: 2011-12-05
• [Presentation] MEGADOCK:構造情報からの相互作用ネットワーク予測 (2011)
  • Author(s): 大上雅史, 山本航平, 松崎由理, 内古賀伸之, 石田貴士, 秋山泰
  • Organizer: 生命情報科学若手の会第3回研究会
  • Place of Presentation: 基礎生物学研究所,愛知県
  • Year and Date: 2011-10-15
• [Presentation] 相互作用プロファイルを用いたタンパク質間ドッキングの代表相互作用の探索 (2011)
  • Author(s): 内古閑伸之, 松崎由理, 大上雅史, 広川貴次, 秋山泰
  • Organizer: 第49回日本生物物理学会年会
  • Place of Presentation: 兵庫県立大学姫路書写キャンパス,兵庫県
  • Year and Date: 2011-09-16
• [Presentation] MEGADOCK : a Fast Protein-protein Interaction Prediction System by Exhaustive Docking (2011)
  • Author(s): Matsuzaki Y, Ohue M, Uchikoga N, Ishida T, Akiyama Y
  • Organizer: 12th International Conference on Systems Biology
  • Place of Presentation: ローゼンカーテン会議場,ハイデルベルグ,ドイツ
  • Year and Date: 2011-09-01
• [Presentation] MEGADOCK : An all-to-all protein-protein interaction prediction system based on tertiary structures information (2011)
  • Author(s): Ohue M
  • Organizer: IIT Madras-Tokyo Tech Joint Workshop on Bioinformatics and Large Scale Data Analysis
  • Place of Presentation: インド工科大学マドラス校,チェンナイ,インド(招待講演)
  • Year and Date: 2011-07-15
• [Presentation] ドッキング計算に基づく網羅的タンパク質-RNA間相互作用予測 (2011)
  • Author(s): 大上雅史, 松崎由理, 内古閑伸之, 石田貴士, 秋山泰
  • Organizer: 情報処理学会第25回バイオ情報学研究会
  • Place of Presentation: 琉球大学,沖縄県
  • Year and Date: 2011-06-24
• [Presentation] タンパク質間相互作用予測における可視化手法の開発および予測精度の改善 (2011)
  • Author(s): 山本航平, 大上雅史, 内古閑伸之, 松崎由理, 石田貴士, 秋山泰
  • Organizer: 情報処理学会第25回バイオ情報学研究会
  • Place of Presentation: 琉球大学,沖縄県
  • Year and Date: 2011-06-24
• [Presentation] MEGADOCK : A fast protein-protein interaction prediction system by exhaustive docking (2011)
  • Author(s): Matsuzaki Y, Ohue M, Uchikoga N, Ishida T, Akiyama Y
  • Organizer: The 9th International Workshop on Advanced Genomics
  • Place of Presentation: 一橋記念講堂,東京都
  • Year and Date: 2011-06-13
• [Remarks]
  • URL: http://www.bi.cs.titech.ac.jp/~ohue/
• [Remarks]
  • URL: http://www.bi.cs.titech.ac.jp
• [Remarks]
  • URL: http://www.bi.cs.titech.ac.jp