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

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.