In-Silico Studies of Oncogene Protein with Anti-Cancer Drugs

An oncogene protein (PDB I.D-5P21) has the possible for cause of cancer. In tumour cells, they were often mutated or expressed at very high levels. Mostly normal cells experience a programmed form of death (apoptosis). It is an important and striking target for anticancer drug development and discovery. In this course we have selected about 20 anticancer drugs that target the oncogene protein. However, the appearance of resistance to these anti-cancer drugs reduces the efficiency of the cancer by targeting the oncogene protein. Among the drug resistance, different sites have been identified for binding of the anti-cancer drugs i.e. Gly 13, Gly 15, Val 20, Asp 33 and Lys 117, which are basically important due to their resistance to nearly all the inhibitors in clinical development. A detailed appreciative of drug resistance mechanism to oncogene protein (PDB I.D-5P21) is critical for the design of novel potent agent targeting of oncogene protein of cancer. In this work, firstly we have to performed the molecular docking studies of about 20 anti-cancer drugs to the oncogene protein and calculate the negative binding energy of the docked complex of oncogene protein and anti-cancer drugs, which can be further studied by the simulation interaction. Molecular dynamics studies can be performed by Schrodinger-Desmond, to perform the possible outcomes under in-silico experiments with the oncogene and drug complex. Binding free energy reveals the drug resistance of anticancer and finds the interaction between the active site and substrate of oncogene and cladrabine. These findings can provides useful information for understanding the drug resistance mechanism beside the oncogene protein. This result also provides some latent clues for further design of novel inhibitors that are less suitable for the drug resistance.