Use of Artificial Intelligence in the Design of Small Peptide Antibiotics Effective Against a Broad Spectrum of Highly Antibiotic-Resistant Superbugs

ACS Chem Biol. 2009 Jan 16;4(1):65-74. doi: 10.1021/cb800240j.

Abstract

Increased multiple antibiotic resistance in the face of declining antibiotic discovery is one of society's most pressing health issues. Antimicrobial peptides represent a promising new class of antibiotics. Here we ask whether it is possible to make small broad spectrum peptides employing minimal assumptions, by capitalizing on accumulating chemical biology information. Using peptide array technology, two large random 9-amino-acid peptide libraries were iteratively created using the amino acid composition of the most active peptides. The resultant data was used together with Artificial Neural Networks, a powerful machine learning technique, to create quantitative in silico models of antibiotic activity. On the basis of random testing, these models proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Artificial Intelligence
  • Computer Simulation
  • Drug Design
  • Drug Resistance, Microbial
  • Humans
  • Mice
  • Peptide Library
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Peptides / toxicity
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / pathogenicity

Substances

  • Anti-Bacterial Agents
  • Peptide Library
  • Peptides