Comparative In-Silico Evaluation of Novel Peptide Analogues and Ceftaroline Against Penicillin-Binding Protein 2A in MRSA

Abstract

Staphylococcus aureus that is resistant to 2-lactam is a major health problem in the world and is likely to be a cause of various complications around the globe. This resistance mainly occurs through penicillin-binding protein 2a (PBP2a) which has low affinity to the conventional antibiotics. Even though Ceftaroline has been found to be effective against MRSA, its usefulness is confined by the emergence of PBP2a mutations. The objective of this research was to examine the thesis of whether HH2 and HG4 novel analog peptides exhibit an increased binding affinity to PBP 2a relative to Ceftaroline.PBP2a protein sequence was retrieved and sequence alignment carried out against four clusters of PBP2 to determine the conserved regions. To achieve the correct modeling, physiochemical characterization, secondary and tertiary structure prediction of PBP2a were done. Molecular docking studies were then done to evaluate and compare the binding of Ceftaroline, HH2 and HG4 to the PBP2a active site.The obtained results of molecular docking demonstrated that Ceftaroline was associated with the PBP2a active site with a higher binding affinity and more stable interactions compared to the analog peptides HH2 and HG4. Interactions between the binding energies and essential hydrogen bonding proved that Ceftaroline is high in stability, in the binding pocket.Ceftaroline had a greater binding affinity and molecular interactions with PBP2a than HH2 and HG4. These results indicate that, although there are still resistance problems, Ceftaroline is a better therapeutic choice in MRSA infection compared to the novel analog peptides trying to be tested. The new research must be directed at structural optimization of peptide analogs in order to increase their binding capacity and counteract new resistance.