Towards <i>In Situ</i> Dynamics of DNA-bound Full-Length p53 Tetramer.

ABSTRACT: p53 is the most important tumor suppressor in humans as well as the most frequently mutated gene found in human cancers with ~50% of all human tumors bearing p53 missense mutations that leave p53 inactive. Restoring the p53 activity proved to lead to tumor regression even in advanced tumors in mouse models- and thus, is among the most attractive potential strategies for novel cancer therapy. Full-length p53 (fl-p53) consists of 393 residues and multiple domains; some folded and some disordered. Using crystal structures of folded domains and integrative molecular modelling techniques for disordered domains, we generated the first wild-type fl-p53 tetramer model bound to DNA. When solvated, the system size nears 500K atoms challenging extensive sampling. Using Anton2 supercomputer for micros

SUBMITTER: Demir O 

PROVIDER: S-EPMC12632852 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature