• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pharmacophore modeling using interaction analysis information by Fragment Molecular Orbital method

Research Project

Project/Area Number 18K18150
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Yoshino Ryunosuke  筑波大学, 医学医療系, 助教 (50817575)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsフラグメント分子軌道法 / ファーマコフォアモデリング / IT創薬 / in silico創薬 / ケモインフォマティクス
Outline of Final Research Achievements

In this study, we propose a pharmacophore modeling based on interaction analysis using FMO method in order to improve conventional pharmacophore modeling that does not consider steric hindrance and acquisition of new interactions.
We analyzed the interaction between dihydroorotate dehydrogenase and inhibitor using the FMO method. As a result, we succeeded in performing the pharmacophore modeling with quantum chemical effects such as CH-pi interaction.

Academic Significance and Societal Importance of the Research Achievements

既知の阻害剤の構造式に基づいて設計を行う Ligand-based drug discovery(LBDD)は、スクリーニングのヒット率は高いが、新たな構造式を持った化合物が得にくい特徴がある。また、標的蛋白質の構造に基づく Structure-based drug discovery(SBDD)は、新たな骨格の化合物を得やすいが、スクリーニングのヒット率は LBDD よりも低い傾向がある。本研究では、LBDD の一種であるファーマコフォアに阻害剤と標的タンパク質の構造情報を取り入れた手法を提案することにより、両手法のメリットを取り入れた新たなスクリーニング手法の確立が期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Parallel cascade selection molecular dynamics to screen for protein complexes generated by rigid docking2019

    • Author(s)
      Harada Ryuhei、Yoshino Ryunosuke、Nishizawa Hiroaki、Shigeta Yasuteru
    • Journal Title

      Journal of Molecular Graphics and Modelling

      Volume: 92 Pages: 94-99

    • DOI

      10.1016/j.jmgm.2019.07.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil2019

    • Author(s)
      Yoshino Ryunosuke、Yasuo Nobuaki、Sekijima Masakazu
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 17464-17464

    • DOI

      10.1038/s41598-019-53945-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A prospective compound screening contest identified broader inhibitors for Sirtuin 12019

    • Author(s)
      Chiba Shuntaro et al.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 19585-19585

    • DOI

      10.1038/s41598-019-55069-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Temperature-pressure shuffling outlier flooding method enhances the conformational sampling of proteins2019

    • Author(s)
      Harada Ryuhei、Yoshino Ryunosuke、Nishizawa Hiroaki、Shigeta Yasuteru
    • Journal Title

      Journal of Computational Chemistry

      Volume: 40 Issue: 15 Pages: 1530-1537

    • DOI

      10.1002/jcc.25806

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Compound property enhancement by virtual compound synthesis2018

    • Author(s)
      Arai Naoki、Yoshikawa Shunsuke、Yasuo Nobuaki、Yoshino Ryunosuke、Sekijima Masakazu
    • Journal Title

      Journal of Bioinformatics and Computational Biology

      Volume: 16 Issue: 03 Pages: 1840016-1840016

    • DOI

      10.1142/s0219720018400164

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] キャップ依存性エンドヌクレアーゼの薬剤耐性メカニズムの解明2019

    • Author(s)
      Yoshino Ryunosuke、Yasuo Nobuaki、Sekijima Masakazu
    • Organizer
      第46回生体分子科学討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Investigation of drug resistance acquisition mechanism of influenza cap-dependent endonuclease against Baloxavir marboxil by molecular dynamics simulation2019

    • Author(s)
      Yoshino Ryunosuke、Yasuo Nobuaki、Sekijima Masakazu
    • Organizer
      The Chem-Bio Informatics Society
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分子動力学シミュレーションを用いた標的タンパク質の分子認識機構の解明2019

    • Author(s)
      Yoshino Ryunosuke
    • Organizer
      計算メディカルサイエンス事業部発足キックオフシンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Discovery of a novel inhibitor of spermidine synthase for Chagas' disease by molecular dynamics and docking simulation2018

    • Author(s)
      Yoshino Ryunosuke、Yasuo Nobuaki、Hagiwara Yohsuke、Ishida Takashi、Inaoka Ken Daniel、Amano Yasushi、Tateishi Yukihiro、Ohno Kazuki、Namatame Ichiji、Niimi Tatsuya、Orita Masaya、Kita Kiyoshi、Akiyama Yutaka、Sekijima Masakazu
    • Organizer
      Asia Hub for e-Drug Discovery
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-04-23   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi