An in silico approach towards cancer therapy using tumor PKM2 as target

Abstract

Cancer is a disease that affects major part of the human population. Though, centuries have been spent upon cancer research many aspects of cancer cell are still undiscovered and thus there has been no effective drug designed that can actually cure cancer. Pyruvate Kinase M2 tumor isoform has been used as a target since 1972, when it was first time discovered. Though, after a series of scientific research, no promising results have been found. There is a need of much intensive research upon this protein as, this protein plays a major role in energy generation as well as, generation of macromolecules which are required for cancer cell proliferation. In this project, various small molecule inhibitors were docked with tumor-PKM2, to check whether they can be used to inhibit the particular protein. Different binding/ active sites of the target protein were used to dock with inhibitors using Auto Dock Vina software. The results showed that set of molecules Kaempferol, L-Phosphophenol and Soc3 showed high affinity towards the protein. Also, some of their analogues gave good results. Kaempferol showed high binding efficiency of -7.8Kcal/mol. Quercetin was a ligand that showed highest efficiency of about -8.1 Kcal/mol at all binding sites. The above molecules that showed high binding efficiency can be used as inhibitors of tumor-PKM2, when attached to cancer specific markers.