Docking and Dynamic Simulation Analysis of P-glycoprotein pumps - Responsible for Chemotherapeutic Resistance post-treatment with Urea and β–mercaptoethanol

The designing of cancer chemotherapy has become increasingly sophisticated over years, against disseminated cancer. With increasing advances in research, resistance to these therapies has also been reported over years. Resistance to treatment with anticancer drugs results from a variety of factors including polymorphic variations in patients and genetic differences in tumours. The most common reason for resistance to a broad range of anticancer drugs is influenced by the expression of one or more energy-dependent transporters (p-glycoprotein pumps) that detect and eject anticancer drugs from cells. Deactivating these pumps can help to overcome such resistance. Thus in this current study lead compounds urea and β–mercaptoethanol has been used to alter the structural confirmation of these P-gp (pump proteins) by using molecular docking and dynamic simulation analysis. Urea β–mercaptoethanol can bind to the target protein with best docking scores of -15.5995 -10.0501 respectively. Binding of β – mercaptoethanol caused a considerable perturbation in the backbone of the target protein with RMSD value eventually deviating to approximately 1.3 and urea further deviate the value to approximately 1.6. Furthermore decrease in the intra-molecular hydrogen bonds over the simulation period confirms the secondary structural change thus ceasing the biological activity of the target protein.