Chemical-protein interactome and its application in off-target identification

Interdisciplinary Sciences: Computational Life Sciences volume 3, pages22–30(2011)Cite this article

Abstract

Drugs exert their therapeutic and adverse effects by interacting with molecular targets. Although designed to interact with specific targets in a desirable manner, drug molecules often bind to unexpected proteins (off-targets). By activating or inhibiting off-targets and the associated biological processes and pathways, the resulting chemical-protein interactions can influence drug reaction directly or indirectly. Exploring the relationship between drug and off-targets and the downstream drug reaction can help understand the polypharmacology of the drug, hence significantly advance the drug repositioning pipeline and the application of personalized medicine in understanding and preventing adverse drug reaction. This review summarizes works on predicting off-targets via chemical-protein interactome (CPI), an interaction strength matrix of drugs across multiple human proteins aiming at exploring the unexpected drug-protein interactions, with a variety of computational strategies, including docking, chemical structure comparison and text-mining etc. Effective recall on previous knowledge, de novo prediction and subsequent experimental validation conferred us strong confidence in these methods. Such studies present prospect of large scale in silico methodologies for off-target discovery with low cost and high efficiency.

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  1. Lun Yang

    Present address: Center for Bioinformatics, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Silver Spring, USA

Affiliations

  1. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200030, China

    Lun Yang, Ke-Jian Wang, Li-Shan Wang, Sheng-Ying Qin, Guang He, Jian Chen, Yue Xiao & Lin He

  2. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Lun Yang & Lin He

  3. Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    Anil G. Jegga

  4. Departments of Pediatrics and Computer Science, University of Cincinnati, Cincinnati, OH, 45221, USA

    Anil G. Jegga

  5. Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    Lin He

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Yang, L., Wang, KJ., Wang, LS. et al. Chemical-protein interactome and its application in off-target identification. Interdiscip Sci Comput Life Sci 3, 22–30 (2011). https://doi.org/10.1007/s12539-011-0051-8

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Key words

  • drug repositioning
  • adverse drug reaction
  • chemical-protein interactome
  • off-target
  • off-system