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Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

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Proteomics for Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1647))

Abstract

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.

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Acknowledgments

This work was supported by the Intramural Research Program of the National Library of Medicine. We thank Sunghwan Kim for helpful discussions about PubChem.

Author information

Authors and Affiliations

  1. National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD, 20894, USA

    Alexander Goncearenco, Minghui Li & Benjamin A. Shoemaker

  2. Leloir Institute Foundation, Av Patricias Argentinas 435, Buenos Aires, C1405BWE, Argentina

    Franco L. Simonetti

  3. National Center for Biotechnology Information, National Institutes of Health, 8600 Rockville Pike, Bldg 38A, Room 8S814, Bethesda, MD, 20894, USA

    Anna R. Panchenko

  4. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China

    Minghui Li

Authors
  1. Alexander Goncearenco
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  2. Minghui Li
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  3. Franco L. Simonetti
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  4. Benjamin A. Shoemaker
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  5. Anna R. Panchenko
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Corresponding author

Correspondence to Anna R. Panchenko .

Editor information

Editors and Affiliations

  1. Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA

    Iulia M. Lazar

  2. Department of Pharmaceutical Sciences, School of Pharmacy, Southern Illinois University Edwardsville, Edwardsville, Illinois, USA

    Maria Kontoyianni

  3. ImmunoGen, Waltham, Massachusetts, USA

    Alexandru C. Lazar

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Goncearenco, A., Li, M., Simonetti, F.L., Shoemaker, B.A., Panchenko, A.R. (2017). Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows. In: Lazar, I., Kontoyianni, M., Lazar, A. (eds) Proteomics for Drug Discovery. Methods in Molecular Biology, vol 1647. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7201-2_15

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  • DOI: https://doi.org/10.1007/978-1-4939-7201-2_15

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7200-5

  • Online ISBN: 978-1-4939-7201-2

  • eBook Packages: Springer Protocols

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