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Photo Marie Skepö

Marie Skepö

Professor

Photo Marie Skepö

Exploring the Functional Landscape of the p53 Regulatory Domain : The Stabilizing Role of Post-Translational Modifications

Author

  • Michael J. Bakker
  • Oskar Svensson
  • Henrik V. So̷rensen
  • Marie Skepö

Summary, in English

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.

Department/s

  • Computational Chemistry
  • MAX IV Laboratory
  • MAX IV, Diffraction and scattering
  • NanoLund: Centre for Nanoscience
  • eSSENCE: The e-Science Collaboration
  • LTH Profile Area: Nanoscience and Semiconductor Technology
  • LUNARC, Centre for Scientific and Technical Computing at Lund University

Publishing year

2024-07

Language

English

Pages

5842-5853

Publication/Series

Journal of Chemical Theory and Computation

Volume

20

Issue

14

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Theoretical Chemistry (including Computational Chemistry)
  • Biological Sciences

Status

Published

ISBN/ISSN/Other

  • ISSN: 1549-9618