Molecular modeling on pyruvate phosphate dikinase of entamoeba histolytica and In silico virtual screening for novel inhibitors

Inhibiting the function of Pyruvate phospate dikinase (PPDK), the key enzyme essential for the glycolytic pathway of Entamoeba histolytica could control the wide spread of intestinal infections caused by this organism. With this objective, we modeled the three dimensional structure of the PPDK protein using the homology-modeling approach. Experimental proof available in literature along with the in silico studies indicated Lys21, Arg91, Asp323, Glu325 and Gln337 to be the probable active sites in the target protein. Virtual screening was carried out using the Genetic docking algorithm GOLD and a consensus scoring function X-Score to substantiate the prediction. The small molecule libraries (ChemDivision database, Diversity dataset, Kinase inhibitor database) were used for screening process. Along with the high scoring results, the interaction studies provided promising ligands for future experiemental screening to inhibit the function of PPDK in Entamoeba histolytica.