In silico and physico-chemical characterization of cluster formation dynamics in peptide solutions

Area of Science:

• Biochemistry
• Microbiology
• Biophysics

Background:

• Antimicrobial peptides (AMPs) show promise against multidrug-resistant bacteria.
• The aggregation behavior and collective phenomena of AMPs are not fully understood.
• Understanding AMP mechanisms is crucial for developing new antibiotics.

Purpose of the Study:

• To investigate the dynamics and bioactivity of nano-cluster formation in novel AMPs.
• To explore the impact of peptide aggregation on antibacterial efficacy.
• To reveal potential synergies in AMP action.

Main Methods:

• In silico molecular dynamics simulations.
• In vitro biophysical techniques (UV-Vis, fluorescence spectroscopy).
• Antibacterial activity assays against *Escherichia coli* and *Bacillus subtilis*.

Main Results:

• Confirmed that aggregation processes significantly impact peptide biological activity.
• Observed spontaneous formation of nano-sized unstructured peptide clusters.
• Demonstrated varying effects of aggregation on different bacterial strains.

Conclusions:

• Peptide aggregation plays a key role in the antimicrobial mechanism of action.
• Novel peptides from *Cornu aspersum* mucus exhibit potent antibacterial properties.
• Findings provide insights into AMPs as potential alternatives to conventional antibiotics.