Deciphering\nInternal Regulatory Patterns within the\np53 Core Tetramer: Insights from Community Network Analysis

Gene therapy is one of the most effective\nstrategies for cancer\ntreatment. The p53 protein, commonly known as the “guardian\nof the genome”, plays a critical role in gene activation and\ntumor suppression. Tetramerization of the p53 core domain is an essential\nallosteric process that supports its suppression functions. This letter\npresents a framework to analyze the structure, function, and dynamic\nconnectivity of the p53 tetramer, using community network analysis\nbased on all-atom molecular dynamics simulations. The communities\nwithin the p53 monomer exhibit distinct functional roles, while interactions\nbetween molecules establish a symmetrical network structure. We identified\ndirect evidence of single, double, and multiple pathway regulations\nwithin the p53 tetramer and crucial residue pairs involved in these\nconnections. Our study provides a comprehensive framework to understand\nthe community network of the p53 tetramer, offering new insights into\nthe stable formation of the p53 core tetramer.