Associating Biological Activity and Predicted Structure of Antimicrobial Peptides from Amphibians and Insects

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Antimicrobial peptides (AMPs) are crucial in combating antimicrobial resistance.
• In silico methods accelerate the discovery of novel AMPs with diverse properties.

Purpose of the Study:

• To bioinformatically identify and characterize novel AMP candidates.
• To evaluate the antibacterial activity and toxicity of identified AMPs.
• To explore the relationship between AMP structure and antimicrobial function.

Main Methods:

• Utilized the rAMPage pipeline for in silico AMP discovery from amphibian and insect RNA-seq data.
• Conducted in vitro assays to assess antibacterial activity against pathogens and toxicity to host cells.
• Performed amino acid sequence analysis and predicted 3D structures using ColabFold.

Main Results:

• Identified 51 novel AMP candidates, with 30 belonging to known families (Brevinin-1, Brevinin-2, Nigrocin-2, Apidaecin).
• Demonstrated significant antibacterial activity against Gram-negative and Gram-positive bacteria.
• Observed low toxicity to red blood cells and human cultured cells.
• Found a correlation between helical structures and broad-spectrum antibacterial activity.

Conclusions:

• The rAMPage pipeline effectively identifies bioactive AMPs.
• Predicted helical structures are associated with potent, broad-spectrum antimicrobial activity.
• Novel AMPs show promise as therapeutics against antimicrobial resistance.