Factor Analysis Scale of Generalized Amino Acid Information as the Source of a New Set of Descriptors for Elucidating the Structure and Activity Relationships of Cationic Antimicrobial Peptides

Abstract

AbstractFactor Analysis Scale of Generalized Amino Acid Information (FASGAI), as a new set of amino acid descriptors, reflecting hydrophobicity, alpha and turn propensities, bulky properties, compositional characteristics, local flexibility, and electronic properties, was derived from multi‐dimensional properties of 20 coded amino acids. Quantitative Structure–Activity Relationship (QSAR) analyses on 101 cationic Antimicrobial Peptides (AMPs) with 15 residues were then performed using FASGAI representation, Genetic Algorithm (GA) selection features, and Partial Least Squares (PLS) modeling. It was found that electronic properties of the tenth residue, bulky properties of the seventh residue, hydrophobicity of the twelfth residue, electronic properties of the third residue were highly positively correlated to antibacterial activity, whereas, hydrophobicity of the sixth residue, compositional characteristics of the sixth residue, and hydrophobicity of the tenth residue were highly negatively correlated to antibacterial activity. Analysis of variance demonstrated that a specific sequence rather than an overall sequence of AMPs may be responsible for high activity. Favorable results showed that FASGAI descriptors cherish many distinguished advantages such as plentiful structural information, easy manipulation, straightforward physicochemical meaning, and high characterization competence, and GA for parameter selection is valid in QSAR of antimicrobial peptides studied. These have thus pointed us further into the potential direction of investigation on structures and functions of other various functional peptides.