p53 DNA结合域与抗癌多肽的拉伸分子动力学研究(英文)

Steered Molecular Dynamics of an AnticancerPeptide Interacting With The p53 DNA-binding Domain

研究发现,取自蓝铜蛋白azurin的一段多肽p28能够进入癌细胞,结合到肿瘤抑制因子p53的DNA结合域上,进而增加p53的抗癌能力.本工作中,通过拉伸分子动力学方法,在原子尺度上研究了p28-p53 DBD复合物的解离过程.分析结果显示复合物的解离过程遵循着一定的分离顺序.对解离力的分析以及对沿着解离路径的不可逆做功的计算,使我们能够从复合物的能量地貌中提取有用的信息,而这些信息也决定了复合物的解离过程.

The p28 peptide, derived from the blue copper protein azurin, is known to enhance the anticancer capabilities of the tumor suppressor p53 likely binding to its DNA-binding domain （DBD）. The p28-p53 DBD complex has been investigated by steered molecular dynamics in order to characterize the unbinding process at atomic resolution. We found that the unbinding of the complex follows a candidate pathway with a well-defined detaching sequence between the partners. The analysis of the unbinding force and the calculation of the irreversible work done along several unbinding paths have allowed us to extract information on the energy landscape regulating the unbinding process.