A molecular dynamics and circular dichroism study of a novel synthetic antimicrobial peptide

TL;DR

This study combines molecular dynamics simulations and circular dichroism experiments to analyze the structure and potential membrane interaction mechanism of a novel synthetic antimicrobial peptide, aiming to inform design improvements.

Contribution

It provides the first detailed structural and mechanistic analysis of a newly designed antimicrobial peptide using combined computational and experimental methods.

Findings

Peptide rapidly forms antiparallel beta strands in solution

Circular dichroism confirms beta-sheet structure

Insights into membrane interaction mechanisms are proposed

Abstract

Antimicrobial peptides are a class of small, usually positively charged amphiphilic peptides that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. Antimicrobial peptides are known for their broad-spectrum antimicrobial activity and thus can be used as a basis for a development of new antibiotics against multidrug-resistant bacteria. The most challengeous task on the way to a therapeutic use of antimicrobial peptides is a rational design of new peptides with enhanced activity and reduced toxicity. Here we report a molecular dynamics and circular dichroism study of a novel synthetic antimicrobial peptide D51. This peptide was earlier designed by Loose et al. using a linguistic model of natural antimicrobial peptides. Molecular dynamics simulation of the peptide folding in explicit solvent shows fast formation of two antiparallel beta strands connected by a beta-turn that is confirmed by circular dichroism measurements. Obtained from simulation amphipatic conformation of the peptide is analysed and possible mechanism of its interaction with bacterial membranes together with ways to enhance its antibacterial activity are suggested.