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

Rieloff, Ellen LU and Skepö, Marie LU (2020) In Journal of Chemical Theory and Computation 16(3). p.1924-1935
Abstract

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,... (More)

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.

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publication status
published
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in
Journal of Chemical Theory and Computation
volume
16
issue
3
pages
12 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:32050065
  • scopus:85080968399
ISSN
1549-9618
DOI
10.1021/acs.jctc.9b01190
language
English
LU publication?
yes
id
b27f7113-daf9-420d-932c-e7bf6991a5ba
date added to LUP
2020-03-20 14:42:43
date last changed
2024-06-26 12:17:38
@article{b27f7113-daf9-420d-932c-e7bf6991a5ba,
  abstract     = {{<p>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.</p>}},
  author       = {{Rieloff, Ellen and Skepö, Marie}},
  issn         = {{1549-9618}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{1924--1935}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Chemical Theory and Computation}},
  title        = {{Phosphorylation of a Disordered Peptide - Structural Effects and Force Field Inconsistencies}},
  url          = {{http://dx.doi.org/10.1021/acs.jctc.9b01190}},
  doi          = {{10.1021/acs.jctc.9b01190}},
  volume       = {{16}},
  year         = {{2020}},
}