Deciphering Internal Regulatory Patterns within the p53 Core Tetramer: Insights from Community Network Analysis

Gene therapy is one of the most effective strategies for cancer treatment. The p53 protein, commonly known as the "guardian of the genome", plays a critical role in gene activation and tumor suppression. Tetramerization of the p53 core domain is an essential allosteric process that supports its suppression functions. This letter presents a framework to analyze the structure, function, and dynamic connectivity of the p53 tetramer, using community network analysis based on all-atom molecular dynamics simulations. The communities within the p53 monomer exhibit distinct functional roles, while interactions between molecules establish a symmetrical network structure. We identified direct evidence of single, double, and multiple pathway regulations within the p53 tetramer and crucial residue pairs involved in these connections. Our study provides a comprehensive framework to understand the community network of the p53 tetramer, offering new insights into the stable formation of the p53 core tetramer.