A novel approach to identify shared fragments in drugs and natural products

Akshay Balasubramanya, Ishwor Thapa, Dhundy Bastola, Dario Ghersi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Fragment-based approaches have now become an important component of the drug discovery process. At the same time, pharmaceutical chemists are more often turning to the natural world and its extremely large and diverse collection of natural compounds to discover new leads that can potentially be turned into drugs. In this study we introduce and discuss a computational pipeline to automatically extract statistically overrepresented chemical fragments in therapeutic classes, and search for similar fragments in a large database of natural products. By systematically identifying enriched fragments in therapeutic groups, we are able to extract and focus on few fragments that are likely to be active or structurally important as scaffolds. We show that several therapeutic classes (including antibacterial, antineoplastic, and drugs active on the cardiovascular system, among others) have enriched fragments that are also found in many natural compounds. Further, our method is able to detect fragments shared by a drug and a natural product even when the global similarity between the two molecules is generally low. A further development of this computational pipeline is to help predict putative therapeutic activities of natural compounds, and to help identify novel leads for drug discovery.

Original languageEnglish (US)
Title of host publicationProceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
Editorslng. Matthieu Schapranow, Jiayu Zhou, Xiaohua Tony Hu, Bin Ma, Sanguthevar Rajasekaran, Satoru Miyano, Illhoi Yoo, Brian Pierce, Amarda Shehu, Vijay K. Gombar, Brian Chen, Vinay Pai, Jun Huan
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages575-580
Number of pages6
ISBN (Electronic)9781467367981
DOIs
StatePublished - Dec 16 2015
EventIEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 - Washington, United States
Duration: Nov 9 2015Nov 12 2015

Publication series

NameProceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015

Other

OtherIEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
CountryUnited States
CityWashington
Period11/9/1511/12/15

ASJC Scopus subject areas

  • Software
  • Artificial Intelligence
  • Health Informatics
  • Biomedical Engineering

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  • Cite this

    Balasubramanya, A., Thapa, I., Bastola, D., & Ghersi, D. (2015). A novel approach to identify shared fragments in drugs and natural products. In L. M. Schapranow, J. Zhou, X. T. Hu, B. Ma, S. Rajasekaran, S. Miyano, I. Yoo, B. Pierce, A. Shehu, V. K. Gombar, B. Chen, V. Pai, & J. Huan (Eds.), Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 (pp. 575-580). [7359746] (Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015). Institute of Electrical and Electronics Engineers Inc.. https://doi.org/10.1109/BIBM.2015.7359746