Overlooked short toxin-like proteins: A shortcut to drug design

Michal Linial*, Nadav Rappoport, Dan Ofer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Short stable peptides have huge potential for novel therapies and biosimilars. Cysteine-rich short proteins are characterized by multiple disulfide bridges in a compact structure. Many of these metazoan proteins are processed, folded, and secreted as soluble stable folds. These properties are shared by both marine and terrestrial animal toxins. These stable short proteins are promising sources for new drug development. We developed ClanTox (classifier of animal toxins) to identify toxin-like proteins (TOLIPs) using machine learning models trained on a large-scale proteomic database. Insects proteomes provide a rich source for protein innovations. Therefore, we seek overlooked toxin-like proteins from insects (coined iTOLIPs). Out of 4180 short (<75 amino acids) secreted proteins, 379 were predicted as iTOLIPs with high confidence, with as many as 30% of the genes marked as uncharacterized. Based on bioinformatics, structure modeling, and data-mining methods, we found that the most significant group of predicted iTOLIPs carry antimicrobial activity. Among the top predicted sequences were 120 termicin genes from termites with antifungal properties. Structural variations of insect antimicrobial peptides illustrate the similarity to a short version of the defensin fold with antifungal specificity. We also identified 9 proteins that strongly resemble ion channel inhibitors from scorpion and conus toxins. Furthermore, we assigned functional fold to numerous uncharacterized iTOLIPs. We conclude that a systematic approach for finding iTOLIPs provides a rich source of peptides for drug design and innovative therapeutic discoveries.

Original languageAmerican English
Article number350
Issue number11
StatePublished - Nov 2017

Bibliographical note

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.


  • Antimicrobial peptide
  • ClanTox
  • Comparative proteomics
  • Complete proteome
  • Disulfide bonds
  • Insects
  • Ion channel inhibitor
  • Machine learning
  • Neurotoxin
  • Protein families


Dive into the research topics of 'Overlooked short toxin-like proteins: A shortcut to drug design'. Together they form a unique fingerprint.

Cite this