De novo design of anticancer peptides by ensemble artificial neural networks

Francesca Grisoni, Claudia S. Neuhaus, Miyabi Hishinuma, Gisela Gabernet, Jan A. Hiss, Masaaki Kotera, Gisbert Schneider

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)


Membranolytic anticancer peptides (ACPs) are drawing increasing attention as potential future therapeutics against cancer, due to their ability to hinder the development of cellular resistance and their potential to overcome common hurdles of chemotherapy, e.g., side effects and cytotoxicity. In this work, we present an ensemble machine learning model to design potent ACPs. Four counter-propagation artificial neural-networks were trained to identify peptides that kill breast and/or lung cancer cells. For prospective application of the ensemble model, we selected 14 peptides from a total of 1000 de novo designs, for synthesis and testing in vitro on breast cancer (MCF7) and lung cancer (A549) cell lines. Six de novo designs showed anticancer activity in vitro, five of which against both MCF7 and A549 cell lines. The novel active peptides populate uncharted regions of ACP sequence space.

Original languageEnglish
Article number112
JournalJournal of Molecular Modeling
Issue number5
Publication statusPublished - 5 Apr 2019
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments The authors thank Sarah Haller for technical support. This research was financially supported by the Swiss National Science Foundation (grants no. CRSII2_160699, no. 200021_157190 and no. IZSEZ0_177477). M.H. was financially supported by BTobitate! (Leap for tomorrow)^ study abroad initiative (Japan’s Ministry of Education, Culture, Sports, Science, and Technology [MEXT]).

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.


  • Artificial intelligence
  • Cancer
  • Counterpropagation
  • Machine learning
  • Membranolysis
  • Peptide design
  • A549 Cells
  • Neural Networks, Computer
  • Humans
  • Peptides/chemistry
  • Models, Molecular
  • Neoplasms/drug therapy
  • Antineoplastic Agents/chemistry
  • Machine Learning
  • MCF-7 Cells
  • Cell Proliferation/drug effects


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