Pharmacoinformatics Analysis to Identify Inhibitors Against transposase, an Ally to Develop Antibiotic Resistance in Streptococcus pneumonia

Streptococcus pneumoniae is increasingly drug resistant in recent years and becoming potential threat health hazard. The availability of the complete genomes of the virulent strains paves ways to combat the disease with pharmacoinformatics approaches. Transposase is an enzyme that catalyzes the movement of the transposon to another part of the genome, and helps the organism to develop antibiotic resistance. In the present work, a combined structure and ligand based pharmacophore modeling, virtual structure based ligand screening, molecular docking and molecular dynamics approaches were employed to identify potent inhibitors of S.pneumoniae transposase. The phamacophore models were used to screen the chemical compounds dataset. ADME properties and the toxicity of the screened compounds were analyzed followed by molecular docking. Further molecular dynamics simulation studies were carried out on the docked complex and the analysis shows that the ligand binding is largely guided by domain movements that help the molecule bury deeply inside and compounds remain bound to the key residues of the binding site. Visualization of the transposase-ligand interactions reveals that Lys137 involved in key interactions in addition to Asp184, and Gln119. Further investigations into the antipathogenic potential of the identified compounds may open new avenues for the design more potent inhibitors.