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Updated: Jun 21, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Exploring the Functional Landscape of the p53 Regulatory Domain: The Stabilizing Role of Post-Translational
Michael J Bakker1,2, Oskar Svensson2,3, Henrik V So Rensen2,4
1Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203/8, 500 05 Hradec Králové, Czech Republic.
Abstract:
This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the N-termini of that intrinsically disordered region. The take-home message for the reader is to achieve a detailed understanding of the impact of phosphorylation with respect to (1) the conformational dynamics and flexibility, (2) structural effects, (3) protein interactivity, and (4) energy landscapes and conformational ensembles. Although our model system is the regulatory domain p53 of the tumor suppressor protein p53, this study contributes to understanding the general effects of intrinsically disordered phosphorylated proteins and the impact of phosphorylated groups, more specifically, how minor changes in the primary sequence can affect the properties mentioned above.
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