Descriptors for antimicrobial peptides

A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates.

This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which of these are currently being used in quantitative structure-activity relationship (QSAR) studies for AMP optimization. Additionally, some key commercial computational tools are discussed, and both successful and less successful studies are referenced, illustrating some of the challenges facing AMP scientists. Through examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion.

Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge to peptide drug discovery, enabling successful design of a new generation anti-infective drug molecules. However, if this wonderful scenario is to play out, computational chemists and peptide microbiologists would need to start playing together and not just side by side.