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Phosphorylation of a disordered peptide – structural effects and force field inconsistencies

DOI: 10.1021/acs.jctc.9b01190 DOI Help

Authors: Ellen Rieloff (Lund University) , Marie Skepö (Lund University; LINXS – Lund Institute of Advanced Neutron and X-ray Science)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Chemical Theory And Computation

State: Published (Approved)
Published: February 2020
Diamond Proposal Number(s): 24294

Open Access Open Access

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 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 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 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 helical content in the N-terminal part of the peptide, where the phosphorylated residues reside, in better agreement with circular dichroism results.

Journal Keywords: Peptides and proteins; Molecular mechanics; Conformation; Cell and molecular biology; Post-translational modification

Subject Areas: Chemistry

Instruments: B21-High Throughput SAXS

Added On: 17/02/2020 14:43


Discipline Tags:

Theoretical Chemistry Chemistry

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)