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Photo Marie Skepö

Marie Skepö

Professor

Photo Marie Skepö

Phosphorylation of a Disordered Peptide - Structural Effects and Force Field Inconsistencies

Author

  • Ellen Rieloff
  • Marie Skepö

Summary, in English

Phosphorylation is one of the most abundant types of post-translational modifications of intrinsically disordered proteins (IDPs). This study examines the conformational changes in the 15-residue-long N-terminal fragment of the IDP statherin upon phosphorylation, using computer simulations with two different force fields: AMBER ff99SB-ILDN and CHARMM36m. The results from the simulations are compared with experimental small-angle X-ray scattering (SAXS) and circular dichroism data. In the unphosphorylated state, the two force fields are in excellent agreement regarding global structural properties such as size and shape. However, they exhibit some differences in the extent and type of the secondary structure. In the phosphorylated state, neither of the force fields performs well compared to the experimental data. Both force fields show a compaction of the peptide upon phosphorylation, greater than what is seen in SAXS experiments, although they differ in the local structure. While the CHARMM force field increases the fraction of bends in the peptide as a response to strong interactions between the phosphorylated residues and arginines, the AMBER force field shows an increase of the helical content in the N-terminal part of the peptide, where the phosphorylated residues reside, in better agreement with circular dichroism results.

Department/s

  • Computational Chemistry
  • LINXS - Institute of advanced Neutron and X-ray Science
  • eSSENCE: The e-Science Collaboration

Publishing year

2020-03-10

Language

English

Pages

1924-1935

Publication/Series

Journal of Chemical Theory and Computation

Volume

16

Issue

3

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Biophysics
  • Theoretical Chemistry (including Computational Chemistry)

Status

Published

ISBN/ISSN/Other

  • ISSN: 1549-9618