Computational studies of protegrin antimicrobial peptides: A review

Abstract

Antimicrobial peptides (AMPs) are small, naturally-occurring peptides that exhibit strong antibacterial properties generally believed to be a result of selective bacterial membrane disruption. As a result, there has been significant interest in the development of therapeutic antibiotics based on AMPs; however, the poor understanding of the fundamental mechanism of action of these peptides has largely hampered such efforts. We present a summary of computational and theoretical investigations of protegrin, a particularly potent peptide that is both an excellent model for the mechanism of action of AMPs and a promising therapeutic candidate. Experimental investigations have shed light on many of the key steps in the action of protegrin: protegrin monomers are known to dimerize in various lipid environments; protegrin peptides interact strongly with lipid bilayer membranes, particularly anionic lipids; protegrins have been shown to form pores in lipid bilayers, which results in uncontrolled ion transport and may be a key factor in bacterial death. In this work, we present a comprehensive review of the computational and theoretical studies that have complemented and extended the information obtained from experimental work with protegrins, as well as a brief survey of the experimental biophysical studies that are most pertinent to such computational work. We show that a consistent, mechanistic description of the bactericidal mechanism of action of protegrins is emerging, and briefly outline areas where the current understanding is deficient. We hope that the research reviewed herein offers compelling evidence of the benefits of computational investigations of protegrins and other AMPs, as well as providing a useful guide to future work in this area.

Implicit Membrane Investigation of the Stability of Antimicrobial Peptide β-Barrels and Arcs

“…Protegrin-1 (hereafter called protegrin) is the best-studied AMP of this family, both experimentally (Heller et al 1998; Tang and Hong 2009; Lam et al 2012) and computationally (Bolintineanu and Kaznessis 2011). It forms ion channels in membranes (Mangoni et al 1996; Sokolov et al 1999).…”

De-Novo Design of Antimicrobial Peptides for Plant Protection

“…To point out the relevance of our results the features of the most relevant peptides identified (SP1-1, SP10-2 and SP10-5) are summarized in supplement (Table S5) and compared to the well-characterized natural peptides magainin II and protegrin I [75]–[79]. However, such a comprehensive set of data for plant protection is not available for natural peptides.…”

Scorpion venom as antimicrobial peptides (AMPs): A review article

“…The carpet model propose that AMPs work like detergents, after the AMPs aggregate on the surface of membranes forming carpet structure and reach its defined threshold, the destruction starts and released patched of membrane look like micelles [34,35].…”