In silico Pharmacokinetics & Molecular Dynamics Studies of JAB1/CSN5 Protein and Discovery of Small Potent Drug against Pancreatic Cancer
Pancreatic cancer (PC) is a major problem worldwide and it is the fourth leading cause of cancer-related deaths in developed countries. The global burden of PC is shifting rapidly from developed countries to the developing countries. Treatment against its malignancy still remains a major challenge in oncology as evidenced by the unchanged mortality rate and also a death to incidence ratio of 0.99. There are numerous molecular factors involved in the chemotherapeutic resistance of pancreatic cancer tumors. Jab1 (Jun activation domain binding protein 1), integrated into COP9 signalosome complex (CSN), initially identified as a co-activator of c-jun and also induces degradation of cell cycle inhibitor p27 and tumor suppressor (p53,Smad4) and therefore a new target in cancer therapy. Here our current study involves designing the suitable inhibitors against MPN domain of this protein by insilico approach. In this, a library of designed compounds constructed and virtually screened through TOPKAT/ADMET test. Screened nontoxic drugs were docked with the Jab1/CSN5 receptor protein. Finally, docking results shows a best drug by comparative study of these ligand molecules, which had lowest Cdocker energy, was chosen against Jab1/CSN5 protein. The best molecule identified was further evaluated by molecular dynamics simulation of protein-ligand complex.