Multi-Objective Optimization Accelerates the De Novo Design of Antimicrobial Peptide for Staphylococcus aureus

Int J Mol Sci. 2024 Dec 21;25(24):13688. doi: 10.3390/ijms252413688.

Abstract

Humans have long used antibiotics to fight bacteria, but increasing drug resistance has reduced their effectiveness. Antimicrobial peptides (AMPs) are a promising alternative with natural broad-spectrum activity against bacteria and viruses. However, their instability and hemolysis limit their medical use, making the design and improvement of AMPs a key research focus. Designing antimicrobial peptides with multiple desired properties using machine learning is still challenging, especially with limited data. This study utilized a multi-objective optimization method, the non-dominated sorting genetic algorithm II (NSGA-II), to enhance the physicochemical properties of peptide sequences and identify those with improved antimicrobial activity. Combining NSGA-II with neural networks, the approach efficiently identified promising AMP candidates and accurately predicted their antibacterial effectiveness. This method significantly advances by optimizing factors like hydrophobicity, instability index, and aliphatic index to improve peptide stability. It offers a more efficient way to address the limitations of AMPs, paving the way for the development of safer and more effective antimicrobial treatments.

Keywords: Staphylococcus aureus; antimicrobial peptide; multi-objective optimization; physicochemical properties.

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Peptides* / chemistry
  • Antimicrobial Peptides* / pharmacology
  • Drug Design
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Machine Learning
  • Microbial Sensitivity Tests
  • Staphylococcus aureus* / drug effects

Substances

  • Antimicrobial Peptides
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides