Interaction of p53 with BRC analogs: A comparative design assisted by ZDOCK and CABS-Dock simulation

The mutation in breast cancer susceptibility gene 2 (BRCA2) is often accompanied by a p53 mutation, the interaction between highly conserved BRC motifs in BRCA2 and p53 was found in cancer progression. For understanding the interaction mechanism of p53 and BRC motifs, the key segment of p53, p53(171-192), was selected as the target, and the spatial structure of p53(171-192)/BRC3 was simulated using computing platform "Discovery studio 2016" and CABS-dock server plat to provide the basis for designing BRC analogs. Polypeptides were purified by HPLC in high purity after synthesized through solid-phase method. Circular dichroism spectroscopy was used to investigate interaction between the BRC peptides and p53(171-192). The results showed that the N-terminus of BRC3 interacted with p53(171-192), but the mutations in helix structure of BRC3 significantly affected the solubility of mutants, which may influence on the interaction of the BRC analogs and p53(171-192). The results also indicated that the structure and action site of BRC3 were different from that of BRC2, having a difference in the interaction role of p53. And may provide some helpful information regarding active polypeptides targeting p53, and inspire the rational design of active polypeptides.