Exploring the Role of Globular Domain Locations on an Intrinsically Disordered Region of p53: A Molecular Dynamics Investigation.

ABSTRACT: The pre-tetramerization loop (PTL) of the human tumor suppressor protein p53 is an intrinsically disordered region (IDR) necessary for the tetramerization process, and its flexibility contributes to the essential conformational changes needed. Although the IDR can be accurately simulated in the traditional manner of molecular dynamics (MD) with the end-to-end distance (EE_dist) unhindered, we sought to explore the effects of restraining the EE_dist to the values predicted by electron microscopy (EM) and other distances. Simulating the PTL trajectory with a restrained EE_dist , we found an increased agreement of nuclear magnetic resonance (NMR) chemical shifts with experiments. Additionally, we observed a plethora of secondary structures and contacts that only

SUBMITTER: Bakker MJ 

PROVIDER: S-EPMC10867847 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature