Potential inhibitors of FemC to combat Staphylococcus aureus: virtual screening, molecular docking, dynamics simulation, and MM-PBSA analysis

Abstract

FemC is a methicillin resistance factor involved in the alterations of peptidoglycan and glutamine synthesis in Staphylococcus aureus. To identify the potent antibacterial agents, antibacterial molecules were screened against the predicted and validated FemC model. Based on docking scores, presence of essential interactions with active site residues of FemC, pharmacokinetic, and ADMET properties, six candidates were shortlisted and subjected to molecular dynamics to evaluate the stability of FemC-ligand complexes. Further, per residue decomposition analysis and Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA) analysis confirmed that S15, M16, S17, R31, R43, Q47, K48 and R49 of FemC played a vital role in the formation of lower energy stable FemC-inhibitor(s) complexes. Therefore, in the present study, the reported six molecules (Z317461228, Z92241701, Z30923155, Z30202349, Z2609517102 and Z92470167) may pave the path to design the scaffold of novel potent antimicrobials against S. aureus. Communicated by Ramaswamy H. Sarma