ct9b01190_si_001.pdf (2.52 MB)
Phosphorylation of a Disordered PeptideStructural Effects and Force Field Inconsistencies
journal contribution
posted on 2020-02-25, 11:13 authored by Ellen Rieloff, Marie SkepöPhosphorylation
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.