title: Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of "cryptic" antimicrobial peptides.
abstract: Cationic antimicrobial peptides (CAMPs) are essential components of innate immunity. Here we show that antimicrobial potency of CAMPs is linearly correlated to the product CmHnL where C is the net charge of the peptide, H is a measure of its hydrophobicity and L its length. Exponents m and n define the relative contribution of charge and hydrophobicity to the antimicrobial potency. Very interestingly the values of m and n are strain specific. The ratio n/(m+n) can vary between ca. 0.5 and 1, thus indicating that some strains are sensitive to highly charged peptides, whereas others are particularly susceptible to more hydrophobic peptides. The slope of the regression line describing the correlation "antimicrobial potency"/"CmHnL product" changes from strain to strain indicating that some strains acquired a higher resistance to CAMPs than others. Our analysis provides also an effective computational strategy to identify CAMPs included inside the structure of larger proteins or precursors, which can be defined as "cryptic" CAMPs. We demonstrate that it is not only possible to identify and locate with very good precision the position of cryptic peptides, but also to analyze the internal structure of long CAMPs, thus allowing to draw an accurate map of the molecular determinants of their antimicrobial activity. A spreadsheet, provided in the Supplementary material, allows performing the analysis of protein sequences. Our strategy is also well suited to analyze large pools of sequences, thus significantly improving the identification of new CAMPs and the study of innate immunity.
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Pane
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Durante
authors.affiliation: Department of Chemical Sciences, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Orlando
authors.initials: O
authors.lastname: Crescenzi
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cafaro
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Pizzo
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Varcamonti
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Zanfardino
authors.affiliation: Department of Medicine, Surgery and Dentistry, Università degli Studi di Salerno, Baronissi, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Izzo
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Di Donato
authors.affiliation: Department of Biology, Università degli Studi di Napoli Federico II, Napoli, Italy. Electronic address: notomist@unina.it.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Notomista
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D000596:Amino Acids; D023181:Antimicrobial Cationic Peptides
keywords: Cathelicidins; Innate immunity; Membrane-binding peptides; Protein sequence analysis