Antimicrobial action of the cationic peptide, chrysophsin-3: a coarse-grained molecular dynamics study

Catte, Andrea; Wilson, Mark R.; Walker, Martin; Oganesyan, Vasily S.

Abstract

Antimicrobial peptides (AMPs) are small cationic proteins that are able to destabilize a lipid bilayer structure through one or more modes of action. In this study, we investigate the processes of peptide aggregation and pore formation in lipid bilayers and vesicles by the highly cationic AMP, Chrysophsin-3 (chrys-3), using coarse-grained molecular dynamics (CG-MD) simulations and potential of mean force calculations. We study long 50 μs simulations of chrys-3 at different concentrations, both at the surface of dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylcholine (POPC) bilayers, and also interacting within the interior of the lipid membrane. We show that aggregation of peptides at the surface, leads to pronounced deformation of lipid bilayers, leading in turn to lipid protrusions for peptide : ligand ratios > 1 : 12. In addition, aggregation of chrys-3 peptides within the centre of a lipid bilayer leads to spontaneous formation of pores and aggregates. Both mechanisms of interaction are consistent with previously reported experimental data for chrys-3. Similar results are observed also in POPC vesicles and mixed lipid bilayers composed of the zwitterionic lipid palmitoyloleoylphosphatidylethanolamine (POPE) and the negatively charged lipid palmitoyloleoylphosphatidylglycerol (POPG). The latter are employed as models of the bacterial membrane of Escherichia coli.

Citation

Catte, A., Wilson, M. R., Walker, M., & Oganesyan, V. S. (2018). Antimicrobial action of the cationic peptide, chrysophsin-3: a coarse-grained molecular dynamics study. Soft Matter, 14(15), 2796-2807. https://doi.org/10.1039/c7sm02152f

• Journal Article Type: Article
• Acceptance Date: Feb 10, 2018
• Online Publication Date: Mar 29, 2018
• Publication Date: Apr 21, 2018
• Deposit Date: Feb 15, 2018
• Publicly Available Date: Feb 15, 2018
• Journal: Soft Matter
• Print ISSN: 1744-683X
• Electronic ISSN: 1744-6848
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 15
• Pages: 2796-2807
• DOI: https://doi.org/10.1039/c7sm02152f
• Public URL: https://durham-repository.worktribe.com/output/1339169