Analysis of multiple compound-protein interactions reveals novel bioactive molecules

Hiroaki Yabuuchi, Satoshi Niijima, Hiromu Takematsu, Tomomi Ida, Takatsugu Hirokawa, Takafumi Hara, Teppei Ogawa, Yohsuke Minowa, Gozoh Tsujimoto, Yasushi Okuno

Research output: Contribution to journalArticlepeer-review

114 Citations (Scopus)


The discovery of novel bioactive molecules advances our systems-level understanding of biological processes and is crucial for innovation in drug development. For this purpose, the emerging field of chemical genomics is currently focused on accumulating large assay data sets describing compoundg-protein interactions (CPIs). Although new target proteins for known drugs have recently been identified through mining of CPI databases, using these resources to identify novel ligands remains unexplored. Herein, we demonstrate that machine learning of multiple CPIs can not only assess drug polypharmacology but can also efficiently identify novel bioactive scaffold-hopping compounds. Through a machine-learning technique that uses multiple CPIs, we have successfully identified novel lead compounds for two pharmaceutically important protein families, G-protein-coupled receptors and protein kinases. These novel compounds were not identified by existing computational ligand-screening methods in comparative studies. The results of this study indicate that data derived from chemical genomics can be highly useful for exploring chemical space, and this systems biology perspective could accelerate drug discovery processes.

Original languageEnglish
Article number472
JournalMolecular Systems Biology
Publication statusPublished - 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics


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