Structure-Based Design of PDHK2 Inhibitors from Docking Studies
Rita Kakkar · 2011
The binding site of dichloroacetate (DCA) in PDHK2 has been examined in detail. As pyruvate is known t o bind at the same site, it has been docked at that site and the interactions responsible for its binding are examin ed. DCA is found to bind more strongly than pyruvate but because of toxicity it is not suitable as a drug. In order to find a m ore suitable ligand, a virtual library of small drug-like molecules is cre ated and various structural, electronic and topolog ical parameters calculated for the ligands correlated with various scoring parameters. Similar calculations are done w ith molecules similar to pyruvate and DCA. of a total of around 2000 mole cules screened this way, a few have been short-list ed, based on their strong binding affinity to PDHK2 and the absence of any serious ADME issues. They have been tested for inhibitor activity and found to be more potent than DCA.