title: QSAR modeling of the antimicrobial activity of peptides as a mathematical function of a sequence of amino acids.
abstract: Antimicrobial peptides have emerged as new therapeutic agents for fighting multi-drug-resistant bacteria. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Therefore, computational techniques had to be applied for process optimization. In this work, the representation of the molecular structure of peptides (mastoparan analogs) by a sequence of amino acids has been used to establish quantitative structure-activity relationships (QSARs) for their antibacterial activity. The data for the studied peptides were split three times into the training, calibration and test sets. The Monte Carlo method was used as a computational technique for QSAR models calculation. The statistical quality of QSAR for the antibacterial activity of peptides for the external validation set was: n=7, r(2)=0.8067, s=0.248 (split 1); n=6, r(2)=0.8319, s=0.169 (split 2); and n=6, r(2)=0.6996, s=0.297 (split 3). The stated statistical parameters favor the presented QSAR models in comparison to 2D and 3D descriptor based ones. The Monte Carlo method gave a reasonably good prediction for the antibacterial activity of peptides. The statistical quality of the prediction is different for three random splits. However, the predictive potential is reasonably well for all cases. The presented QSAR modeling approach can be an attractive alternative of 3D QSAR at least for the described peptides.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita'degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Mariya A
authors.initials: MA
authors.lastname: Toropova
authors.affiliation: University of Niš, Faculty of Medicine, Department of Chemistry, Bulevar Dr Zorana Đinđića 81, 18000 Niš, Serbia. Electronic address: aveselinovic@medfak.ni.ac.rs.
authors.forename: Aleksandar M
authors.initials: AM
authors.lastname: Veselinović
authors.affiliation: University of Niš, Faculty of Medicine, Department of Chemistry, Bulevar Dr Zorana Đinđića 81, 18000 Niš, Serbia.
authors.forename: Jovana B
authors.initials: JB
authors.lastname: Veselinović
authors.affiliation: University of Niš, Faculty of Medicine, Public Health Institute Niš, 18000 Niš, Serbia.
authors.forename: Dušica B
authors.initials: DB
authors.lastname: Stojanović
authors.affiliation: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, 20156, Via La Masa 19, Milano, Italy.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Toropov
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009010:Monte Carlo Method; D019151:Peptide Library; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D019151:Peptide Library
keywords: Antimicrobial activity; CORAL software; Mastoparan analogs; Monte Carlo method; Optimal descriptor; QSAR