Computational design of prospective molecular targets for Burkholderia cepacia complex by molecular docking and dynamic simulation studies

The study aimed to screen prospective molecular targets of BCC and potential natural lead candidates as effective binders by computational modeling, molecular docking, and dynamic (MD) simulation studies. Based on the virulent functions, tRNA 5‐methylaminomethyl‐2‐thiouridine biosynthesis bifunctional protein (mnmC) and pyrimidine/purine nucleoside phosphorylase (ppnP) were selected as the prospective molecular targets. In the absence of experimental data, the three‐dimensional (3D) structures of these targets were computationally predicted. After a thorough literature survey and database search, the drug‐likeness, and pharmacokinetic properties of 70 natural molecules were computationally predicted and the effectual binding of the best lead molecules against both the targets was predicted by molecular docking. The stabilities of the best‐docked complexes were validated by MD simulation and the binding energy calculations were carried out by MM‐GBSA approaches. The present study revealed that the hypothetical models of mnmC and ppnP showed stereochemical accuracy. The study also showed that among 70 natural compounds subjected to computational screening, Honokiol (3′,5‐Di(prop‐2‐en‐1‐yl) [1,1′‐biphenyl]‐2,4′‐diol) present in Magnolia showed ideal drug‐likeness, pharmacokinetic features and showed effectual binding with mnmC and ppnP (binding energies −7.3 kcal/mol and −6.6 kcal/mol, respectively). The MD simulation and GBSA calculation studies showed that the ligand‐protein complexes stabilized throughout tMD simulation. The present study suggests that Honokiol can be used as a potential lead molecule against mnmC and ppnP targets of BCC and this study provides insight into further experimental validation for alternative lead development against drug resistant BCC.