Computational bioprospecting of phytoconstituents as potential inhibitors for peptide deformylase from Streptococcus oralis: An opportunistic pathogen.

ABSTRACT

Streptococcus oralis an opportunistic bacterium has been reported to be involved in various blood borne infections like subacute bacterial endocarditis, septicemia, bacterial meningitis and in some cases dental caries too. Among various targets the peptide deformylase, of S.oralis appears to be most potent druggable target as it is involved in protein synthesis is opted for the current study. Due to unavailability of PDB structure of peptide deformylase from S. oralis the study initiates with homology modelling of the protein and 6OW2 of S pneumoniae is considered as the template. Thereafter, Molecular docking, Molecular dynamic simulation, ADME analysis, and MMPBSA analysis was carried out to explore the inhibitory potential of phyto-constituents as potential inhibitors for Peptide deformylase from S.oralis. Actinonin was considered as reference drug. Among 2370 phyto compounds the best observations were recorded for A1-Barrigenol (IMPHY010984) with binding affinity of -8.5 kcal/mol. Calculated RMSD, RMSF, Binding Free Energy for IMPHY010984 averaged at about 0.10 ± 0.03 nm, 0.08 ± 0.05 nm, 131 ± 21 kJ/mol respectively whereas the RMSD, RMSF, Binding Free Energy recorded for reference drug averaged at about 0.19 ± 0.04 nm, 0.11 ± 0.08 nm, -94 ± 18 kJ/mol respectively. Based on in silico observations IMPHY010984 is proved out as superior candidate over reference drug. The study reflects the potential of IMPHY010984 as prophylactic therapeutics for S.oralis.