Abstract:
The p53 protein is a vital natural agent that suppresses the cancer cells. This protein exist in a
mutual loop with its inhibitor, the Mdm2 protein. Because this protein is a suppressor protein
so, Mdm2 protein regulate its levels. In majority of tumors this protein is absent. This is
because of the hyper-active concentration of Mdm2 protein. Nutlin-3a, a novel drug, is used
to control the hyper-activity of Mdm2 protein. The binding properties of the drug are
responsible for breaking the loop between the p53 and the Mdm2 protein. This protein
occupies p53 pocket, consequently, the loop becomes dysfunctional.
In this work, we have aimed to activate the p53 protein using the novel drug, nutlin-3a. For
this purpose, we have adapted control system methods and selected three different techniques
to design a dosage strategy in order to activate the p53 protein. The performance of all the
techniques have been analyzed using the In-Silico trails. The results obtained from all the
techniques have been compared. In order to have a fair comparison, the desired and the
measured outputs are kept same for all the techniques.
The result obtained using the In-Silico trails shows that all the techniques were able to
activate the p53 protein. Moreover, the hyper-activity of Mdm2 protein is regulated to its
desired level, i.e. its equilibrium point. In the case of PID controller, the error reduces to
zero. However, the h-infinity controller provides an insight to the performance robustness of
the system. Overall, the results obtained in the case of feedback linearization are
comparatively better as it provides the minimum peak of p53 protein. In addition to it, the
stability of internal dynamics of the system is also ensured using the design of feedback
linearization. A suitable Lyaponuv candidate function is selected to stabilize the system.
