Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. There are four mammalian pyruvate kinase isoforms (PKM1, PKM2, PKR, PKL), and each isoform has had multiple designations over time in the literature. PKM2 is the embryonic isoform and is expressed in cancer. PKM2 is a key enzyme in glycolytic pathway control at the tumor cell metabolism. The inhibition of the PKM2 decreases the growth and the proliferation of cancer cells. Lapachol is a phenolic compound and a PKM2 inhibitor having anticarcinogenic properties however it has foetotoxic effects hence, new synthetic derivatives need to be developed for targeting cancer. In the present research proposal, we would design and perform in-silico evaluation of PKM2 inhibitors based on Lapachol using DoG Site Scorer, SeeSAR, infiniSee, FlexX , PoseView & Molecular Dynamics of the Ligand-PKM2 complex using GROMACS.
Sailendra Kumar intends to achieve the following milestones:
- Estimation of binding energy Lapachol for PKM2 and Design of PKM2 inhibitors based on Lapachol.
- Filtration of designed drug molecules and Docking study of designed PKM2 inhibitors.
- Identification of binding site residues at the binding site of inhibitor and Molecular dynamics simulation of the lead molecule.