Physicochemical Features and Peculiarities of Interaction of Antimicrobial Peptides with the Membrane

TL;DR

This paper reviews the physicochemical features and interaction mechanisms of antimicrobial peptides with cell membranes, emphasizing their importance for designing new peptide-based antibiotics.

Contribution

It provides a comprehensive review of AMP physicochemical properties and their role in membrane interaction, aiding in the development of predictive models for de novo antibiotic design.

Findings

Physicochemical features determine AMP classification.

Hydrophobicity and amphiphilicity are key to AMP activity.

Physicochemical knowledge enables targeted peptide design.

Abstract

Antimicrobial peptides (AMPs) are anti-infectives that have potential as a novel and untapped class of biotherapeutics. Modes of action of antimicrobial peptides imply interaction with cell envelope. Comprehensive understanding of peculiarities of interactions of antimicrobial peptides with cell envelope is necessary to perform the task-oriented design of new biotherapeutics, against which for microbes it is hard to work out resistance. In order to enable a de novo design with low costs and in high throughput, in silico predictive models have to be required. To develop the performant predictive model, comprehensive knowledge on mechanisms of action of AMPs has to be possessed. The last knowledge will allow us to encode amino acid sequences expressively and to get success to the choosing of the accurate classifier of AMPs. A shared protective layer of microbial cells is inner, plasmatic membrane. The interaction of AMP with a biological membrane (native and/or artificial) is the most comprehensively studied. We provide a review of mechanisms and results of interaction of AMP with the cell membrane, relying on the survey of physicochemical, aggregative and structural features of AMPs. Potency and mechanism of action of AMP have presented in the terms of amino acid compositions and distributions of the polar and apolar residues along the chain, that is in such physicochemical features of peptides as the hydrophobicity, hydrophilicity, and amphiphilicity. Many different approaches were used to classify AMPs. The survey of the knowledge on sequences, structures, and modes of actions of AMP, allows concluding that, only the physicochemical features of AMPs give the capability to perform the unambiguous classification. Comprehensive knowledge of physicochemical features of AMP is necessary to develop task-oriented methods of design of peptide-based antibiotics de novo.