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Development and application of a conformational search model to predict three-dimensional structural ensembles of glycans

Research Project

Project/Area Number 16K00415
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Life / Health / Medical informatics
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Re Suyong  国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (50390670)

Research Collaborator SUGITA Yuji  
YAMAGUCHI Yoshiki  
GALVELIS Raimondas  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖鎖 / 立体構造アンサンブル / 分子動力学シミュレーション / レプリカ交換法 / 拡張アンサンブル法 / N型糖鎖 / 立体構造予測 / 分子動力学計算 / メタダイナミクス / メタダイナミクス法
Outline of Final Research Achievements

Glycan is a biomolecule in which monosaccharides are linked through glycosidic linkages. Glycans bind to proteins as well as lipids and are involved in a various biological process, and also relate to diseases such as viral infections. Three-dimensional structural information of glycans is essential for understanding and controlling glycans' functions. However, 3D-structures of glycans are difficult to obtained by experiment due to the complexity and flexibility of their structures.
In this work, we present a powerful means to computationally predict 3D-structural ensembles (a structural model consisting of multiple three-dimensional structures that represent flexible biomolecular structures) of glycans. We show that, using a combined method of replica exchange molecular dynamics with metadynamics, it is possible to enhance the conformational sampling of glycans and to predict 3D-structural ensembles of N-glycans in high precision.

Academic Significance and Societal Importance of the Research Achievements

DNAやRNA、タンパク質については、構造生物学的な研究により機能と構造との関係が次々と明らかになり、それらの理解・情報を用いて薬剤分子も設計されている。一方で、糖鎖の構造は柔らかく複雑であるため、機能に関係する構造情報を得るのが極めて難しい。本研究成果は、計算化学の手法を用いた糖鎖立体構造予測の強力な手段を提供するもので、糖鎖の構造―機能相関を解明する推進力となるとともに、新たな創薬ターゲットの創出にも繋がると期待する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Book (1 results)

  • [Journal Article] Population shift mechanism for partial agonism of AMPA receptor2019

    • Author(s)
      Oshima H, Re S, Sakakura M, Takahashi H, Sugita Y.
    • Journal Title

      Biophys. J.

      Volume: 116 Issue: 1 Pages: 52-68

    • DOI

      10.1016/j.bpj.2018.11.3122

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular dynamics of glycan2019

    • Author(s)
      Suyong Re, Yoshiki Yamaguchi, Yuji Sugita
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Conformational Ensembles of Protonated N-glycans in the Gas-Phase2018

    • Author(s)
      Re Suyong、Watabe Shigehisa、Nishima Wataru、Muneyuki Eiro、Yamaguchi Yoshiki、MacKerell Alexander D.、Sugita Yuji
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1644-1644

    • DOI

      10.1038/s41598-018-20012-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced Conformational Sampling of N-Glycans in Solution with Replica State Exchange Metadynamics2017

    • Author(s)
      Raimondas Galvelis, Suyong Re, and Yuji Sugita
    • Journal Title

      Journal of Chemical Theory and Computation

      Volume: 13 Issue: 5 Pages: 1934-1942

    • DOI

      10.1021/acs.jctc.7b00079

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Revealing Drug-Target Binding Pathway using Two-dimensional Replica-Exchange Molecular Dynamics Method2019

    • Author(s)
      Suyong Re, Hiraku Oshima, Kento Kasahara, Motoshi Kamiya, and Yuji Sugita
    • Organizer
      The 1st R-CCS International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] レプリカ交換法を用いたタンパク質ーリガンド結合計算2019

    • Author(s)
      李秀栄
    • Organizer
      第2回近畿大学先端技術総合研究所高圧力蛋白質研究センターセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Extensive molecular dynamics sampling characterizes ligand binding pathway to Src kinase2018

    • Author(s)
      李 秀栄, 尾嶋 拓, 神谷 基司, 杉田 有治
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ダイナミックドッキングによる結合親和性予測2018

    • Author(s)
      李秀栄
    • Organizer
      CBI学会2018年大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 拡張アンサンブル法に基づく細胞膜受容体・リガンド結合の自由エネルギー解析2018

    • Author(s)
      李 秀栄, 尾嶋 拓, 新津 藍, 杉田 有治
    • Organizer
      第5回 「京」を中核とするHPCIシステム利用研究課題成果報告会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分子動力学シミュレーションによる生体分子機能モデリング2018

    • Author(s)
      李秀栄
    • Organizer
      第1回近畿大学生物理工学部HPCシンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] REMD-based flexible docking2018

    • Author(s)
      Suyong Re, Hiraku Oshima, Motoshi Kamiya, and Yuji Sugita
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] イオンモビリティー質量分析における衝突断面積の物理化学的な決定因子2017

    • Author(s)
      李 秀栄、渡部 茂久、二島 渉、宗行 英朗、山口 芳樹、 杉田 有治
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] レプリカ交換分子動力学法を用いたフレキシブルドッキング2017

    • Author(s)
      李秀栄
    • Organizer
      第3回 ポスト「京」重点課題1ワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] Incorporation of protein flexibility into ligand binding simulation2017

    • Author(s)
      Suyong Re, Hiraku Oshima, Motoshi Kamiya, and Yuji Sugita
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Flexible Docking using Replica-Exchange Molecular Dynamics Simulation2017

    • Author(s)
      李秀栄
    • Organizer
      CBI学会2017年大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] グライコフォームを予測する革新的理論化学2016

    • Author(s)
      李秀栄
    • Organizer
      第35回日本糖質学会年会
    • Place of Presentation
      高知市文化プラザ(高知)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Modeling flexible biomolecules by MD simulations with enhanced sampling2016

    • Author(s)
      李秀栄、杉田有治
    • Organizer
      RIKEN QBiC Retreat 2016
    • Place of Presentation
      淡路夢舞台国際会議場(淡路)
    • Year and Date
      2016-06-20
    • Related Report
      2016 Research-status Report
  • [Book] Biomolecular Simulations: Methods and Protocols2019

    • Author(s)
      Yuji Sugita, Motoshi Kamiya, Hiraku Oshima, Suyong Re
    • Publisher
      Springer
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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