A significant loss of p53 protein, an anti-tumour agent, is observed in early cancerous cells. Induction of small molecules based drug is by far the most prominent technique to revive and maintain wild-type p53 to the desired level. In this study, a sliding mode control (SMC) based robust non-linear technique is presented for the drug design of a control-oriented p53 model. The control input generated by conventional SMC is discontinuous; however, depending on the physical nature of the system, drug infusion needs to be continuous. Therefore, to obtain a smooth control signal, a dynamic SMC (DSMC) is designed. Moreover, the boundedness of the zero-dynamics is also proved. To make the model-based control design possible, the unknown states of the system are estimated using an equivalent control based, reduced-order sliding mode observer. The robustness of the proposed technique is assessed by introducing input disturbance and parametric uncertainty in the system. The effectiveness of the proposed control scheme is witnessed by performing in-silico trials, revealing that the sustained level of p53 can be achieved by controlled drug administration. Moreover, a comparative quantitative analysis shows that both controllers yield similar performance. However, DSMC consumes less control energy.

中文翻译：

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p53 通路的滑模控制器-观察者对。

在早期癌细胞中观察到 p53 蛋白（一种抗肿瘤剂）的显着损失。基于小分子的药物诱导是迄今为止将野生型 p53 恢复并维持至所需水平的最突出的技术。在本研究中，提出了一种基于滑模控制 (SMC) 的鲁棒非线性技术，用于面向控制的 p53 模型的药物设计。传统SMC产生的控制输入是不连续的；然而，根据系统的物理性质，药物输注需要连续。因此，为了获得平滑的控制信号，设计了动态SMC（DSMC）。此外，还证明了零动力学的有界性。为了使基于模型的控制设计成为可能，系统的未知状态使用基于等效控制的降阶滑模观测器进行估计。通过在系统中引入输入干扰和参数不确定性来评估所提出技术的鲁棒性。通过进行计算机试验证明了所提出的控制方案的有效性，表明p53的持续水平可以通过控制药物施用来实现。此外，比较定量分析表明，两种控制器具有相似的性能。然而，DSMC 消耗的控制能量较少。