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2017 Fiscal Year Annual Research Report

A new rotation-translation invariant molecular encoding and its use in Computer-Aided Drug-Discovery

Research Project

Project/Area Number 17F17051
Research InstitutionKyushu University

Principal Investigator

山西 芳裕  九州大学, 生体防御医学研究所, 准教授 (60437267)

Co-Investigator(Kenkyū-buntansha) BERENGER FRANCOIS  九州大学, 生体防御医学研究所, 外国人特別研究員
Project Period (FY) 2017-07-26 – 2019-03-31
KeywordsLBVS / QSAR / applicability domain
Outline of Annual Research Achievements

I have created a rotation-translation invariant encoding of 3D molecular surfaces. It works in a combination of the shape, the hydrophobic, the hydrogen bond donor and acceptor spaces. I have published two articles during this year. I am currently writing an article with my host researcher on a fully automatic applicability domain algorithm. Most previous methods were not fully automatic because they involve a critical user-chosen parameter. Our algorithm boosts classification performance of Quantitative Structure Activity Relationship models. I have written several programs and libraries for chemoinformatics research. Some of them were released as open source. I have also done some QSAR modeling for the CFTR protein target (involved in cystic fibrosis) to select molecules for purchase.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

The research is going well since we already got some interesting results (our new applicability domain algorithm) and we could apply our expertise to a real-world drug-discovery project by doing some QSAR modeling. We have also created several open source libraries for chemoinformatics: bisec-tree (a bisector tree to index molecules), parany (a library to parallelize stream computing) (many chemoinformatics tasks work on a stream of molecules), and cpmlib (more metrics were added in our classification performance metrics library). We have wrapped SVMs and gradient boosting to use with our programming language of choice (OCaml). Thanks to our work in OCaml for chemoinformatics, we have been invited to an upcoming special issue on programming languages for the journal of
chemoinformatics.

Strategy for Future Research Activity

Our current encoding of 3D surfaces is too slow for chemoinformatics standards. Also, in ligand-based virtual screening experiments, combining the four spaces only outperforms by a small margin well established 2D fingerprints like MACCS or ECFP4. Moreover, the current encoding does not allow to go from proteins to
ligands or the reverse. I will refocus my work in 2D. The encoding will work at a higher abstraction level
(with atoms instead of discrete surfaces) and I will use existing software to extract protein-ligand interactions. I will also use existing databases of protein-ligand complexes in order to access a significant amount of high quality data. Maybe, once the descriptor is satisfactorily working in 2D, it will allow us to better understand if and how to extend it to 3D.

  • Research Products

    (5 results)

All 2018 2017

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

  • [Journal Article] Fragger: a protein fragment picker for structural queries2018

    • Author(s)
      Berenger Francois、Simoncini David、Voet Arnout、Shrestha Rojan、Zhang Kam Y.J.
    • Journal Title

      F1000Research

      Volume: 6 Pages: 1722~1722

    • DOI

      10.12688/f1000research.12486.2

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Consensus queries in ligand-based virtual screening experiments2017

    • Author(s)
      Berenger Francois、Vu Oanh、Meiler Jens
    • Journal Title

      Journal of Cheminformatics

      Volume: 9 Pages: 60

    • DOI

      10.1186/s13321-017-0248-5

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Consensus queries in ligand-based virtual screening experiments2017

    • Author(s)
      Francois Berenger
    • Organizer
      Society of Computer Chemistry Japan (SCCJ), 2017 fall meeting
    • Invited
  • [Presentation] A new rotation-translation invariant molecular descriptor for Ligand-Based Virtual Screening and beyond2017

    • Author(s)
      Francois Berenger and Yoshihiro Yamanishi
    • Organizer
      Chem-Bio Informatics Society(CBI) Annual Meeting 2017
  • [Presentation] A new rotation-translation invariant molecular descriptor for Ligand-Based Virtual Screening and beyond2017

    • Author(s)
      Francois Berenger and Yoshihiro Yamanishi
    • Organizer
      Informatics In Biology, Medicine and Pharmacology (IIBMP) 2017

URL: 

Published: 2018-12-17  

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