Hidden electrostatic energy contributions define dynamic allosteric communications within p53 during molecular recognition.

ABSTRACT: Molecular recognition is fundamental to transcription regulation. As a transcription factor, the tumor suppressor p53 has to recognize either specific DNA sequences or repressor protein partners. However, the molecular mechanism underlying the p53 conformational switch from the DNA-bound to repressor-bound states is not fully characterized. The highly charged nature of these interacting molecules prompted us to explore the nonbonded energy contributions behind molecular recognition of either a DNA or the repressor protein iASPP by p53 DNA binding domain (p53DBD), using molecular dynamics simulation followed by rigorous analyses of energy terms. Our results illuminate the allosteric pathway by which iASPP binding to p53 diminishes binding affinity between p53 and DNA. Even though the p53DBD

SUBMITTER: Bhattacharjee S 

PROVIDER: S-EPMC8553636 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature