Enhanced Interaction of Shuffled Mutacin IV, an Antimicrobial Peptide of Bacterial Origin, with Surface Protein IsdB of Staphylococcus aureus

• Published in: International journal of peptide research and therapeutics Vol. 20; no. 1; pp. 71 - 76
• Main Authors: Jain, Chakresh K., Sethi, Raman, Sharma, Vanashika, Mathur, Ashwani, Sharma, Sanjeev K.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2014; Springer Nature B.V
• Subjects: Animal Anatomy; Antimicrobial agents; Biochemistry; Biomedical and Life Sciences; Histology; Life Sciences; Molecular Medicine; Morphology; Pathogens; Peptides; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Polymer Sciences; Proteins; Net charge; In vitro aggregation; Randomization; Docking; In vivo aggregation; Hydrophobicity; Antimicrobial peptide
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-013-9368-6

Antimicrobial peptides are produced by prokaryotes and eukaryotes with fundamental role of protection against pathogenic microbes. Staphylococcus aureus , a major virulent pathogen in humans, shows multiple drug resistance and is affected by the bacteriocin activity of Mutacin IV. Currently, peptide therapeutics has been reported as a potential alternative for treating microbial infections specially exhibiting multiple drug resistance. However, the mechanism of action and interaction of peptides with target proteins is not known. The current work is an attempt to address the above issue by performing molecular docking and randomization experiments. In this study, antimicrobial peptides of bacterial origin (168 peptides) were collected from APD2 database and their net charge and hydrophobicity values were retrieved. Mutacin IV (APD Id—AP01174), a 44 amino acids long peptide derived from Streptococcus mutans UA140, was selected on the basis of high hydrophobicity to net charge ratio (0.52) and used for in silico docking studies with therapeutically important surface proteins viz. IsdA, IsdB, ClfB, and SasG of S. aureus using ZDOCK server. The docking result of IsdB surface protein and Mutacin IV was found better (ZDOCK score 1168.582) as compared to others. Afterwards, the native Mutacin IV sequence was randomized to generate 50 new combinations using EMBOSS (Shuffleseq) tool. The new sequence of Mutacin IV was screened on the basis of high in vivo to in vitro aggregation ratio (i.e. high in vivo aggregation and low in vitro aggregation values) and good binding energies against IsdB surface protein of S. aureus from the randomized sequences. The new peptide sequence showed an in vivo to in vitro aggregation ratio of 2.206 and 0.888, respectively which is higher than native sequence of Mutacin IV ratio (0.205). Moreover, the ZDOCK scores were found to be 1370.529 and 1687.048 which were better than the native sequence of Mutacin IV (ZDOCK score 1168.582). This research work identifies the new sequence of Mutacin IV peptide which binds effectively to the surface proteins of S. aureus and thereby could be a better peptide than native Mutacin IV. Our finding also demonstrates enhanced interactions of new Mutacin IV peptide with IsdB surface protein to understand the structural implications and proposes its effective antimicrobial role against S. aureus .