Bioinformatics analysis of wild-type ParC and S79F, S79Y mutations in Streptococcus pneumoniae

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Akgün Karapınar D. B., Oflaz O.



OBJECTIVE: S79Y and S79F mutations in ParC at the fluoroquinolone binding site confer resistance to quinolones in Streptococcus pneumoniae. The aim of this study was to perform bioinformatics analysis of wild-type and mutant ParC identified in S. pneumoniae strains.

MATERIALS AND METHODS: Homology models were created with Swiss Model, and the UCSF Chimera was used for the analysis and evaluation of the models. Molecular docking studies and protein-ligand interaction analysis were performed using CB-Dock developed by AutoDock Vina and Protein Ligand Interaction Profiler (PLIP), respectively.

RESULTS: According to the homology modeling results, changes were observed in the physicochemical properties. Both mutant types showed a decrease in hydrophobicity (S79F: 2.0, S79Y: 0.5 – Kyte-Doolittle) and an increase in regional volume (S79F: 95 Å3, S79Y: 100 Å3). The docking scores for the wild-type, S79F, and S79Y types were 6.3, 4.9, and 5.0, respectively. The decrease in docking scores indicates weaker binding in the mutant types. The results of the PLIP analysis indicate that new bonds were formed, and the bond types changed in both mutant types, while some bonds disappeared.

CONCLUSIONS: It is believed that the change in physicochemical properties caused by the mutation altered the conformation of the quinolone binding region and the bond types, numbers, and proximities of the amino acids involved in the interaction with the active substance. The results obtained from the modeling performed in this study with visualization and analysis of possible conformational, hydrophobic, and volumetric changes of only ParC mutations provided data and literature support to elucidate the mechanism. The molecular docking and PLIP results obtained in this study support both the homology modeling results and the fact that S79F and S79Y have been shown to be resistant in the literature.