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

• Published in: Archives of biochemistry and biophysics 2024-08, Vol.758, p.110079, Article 110079
• Main Authors: Sharma, Shrutika, Pandey, Khushhali M.
• Format: Article
• Language: English
• Subjects: Amidohydrolases - antagonists & inhibitors; Amidohydrolases - chemistry; Amidohydrolases - metabolism; bacteria; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; biophysics; blood; chemical constituents of plants; computer simulation; dental caries; drugs; endocarditis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Ethno-medicinal plants; Gibbs free energy; Hydroxamic Acids; meningitis; MMPBSA; Molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; Opportunistic pathogen; opportunistic pathogens; Peptide deformylase; peptides; Phytochemicals - chemistry; Phytochemicals - pharmacology; Plant-based inhibitors; protein synthesis; septicemia; Streptococcus oralis; Streptococcus oralis - drug effects; Streptococcus oralis - enzymology; therapeutics
• ISSN: 0003-9861; 1096-0384; 1096-0384
• DOI: 10.1016/j.abb.2024.110079

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. [Display omitted] •Streptococcus oralis, an opportunistic pathogen is associated with various systemic infections.•Peptide deformylase is crucial for bacterial protein synthesis.•2370 phytoconstituents were tested against peptide deformylase of Streptococcus oralis.•Homology modelling of protein was done followed by molecular docking and molecular dynamics simulation studies.•Study revealed A1-Barrigenol as potent inhibitor of peptide deformylase of Streptococcus oralis.