Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison

Phosphorylation is a common post-translational modification among intrinsically disordered proteins and regions, which helps regulate function by changing the protein conformations, dynamics, and interactions with binding partners. To fully comprehend the effects of phosphorylation, computer simulat...

Full description

Bibliographic Details
Main Authors: Ellen Rieloff, Marie Skepö
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/18/10174
_version_ 1797518863199371264
author Ellen Rieloff
Marie Skepö
author_facet Ellen Rieloff
Marie Skepö
author_sort Ellen Rieloff
collection DOAJ
description Phosphorylation is a common post-translational modification among intrinsically disordered proteins and regions, which helps regulate function by changing the protein conformations, dynamics, and interactions with binding partners. To fully comprehend the effects of phosphorylation, computer simulations are a helpful tool, although they are dependent on the accuracy of the force field used. Here, we compared the conformational ensembles produced by Amber ff99SB-ILDN+TIP4P-D and CHARMM36m, for four phosphorylated disordered peptides ranging in length from 14–43 residues. CHARMM36m consistently produced more compact conformations with a higher content of bends, mainly due to more stable salt bridges. Based on comparisons with experimental size estimates for the shortest and longest peptide, CHARMM36m appeared to overestimate the compactness. The difference between the force fields was largest for the peptide showing the greatest separation between positively charged and phosphorylated residues, in line with the importance of charge distribution. For this peptide, the conformational ensemble did not change significantly upon increasing the ionic strength from 0 mM to 150 mM, despite a reduction of the salt-bridging probability in the CHARMM36m simulations, implying that salt concentration has negligible effects in this study.
first_indexed 2024-03-10T07:35:20Z
format Article
id doaj.art-efa81dbf66894aa48c2d49c1b08d6e8c
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T07:35:20Z
publishDate 2021-09-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-efa81dbf66894aa48c2d49c1b08d6e8c2023-11-22T13:33:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122181017410.3390/ijms221810174Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field ComparisonEllen Rieloff0Marie Skepö1Division of Theoretical Chemistry, Lund University, P.O. Box 124, SE-221 00 Lund, SwedenDivision of Theoretical Chemistry, Lund University, P.O. Box 124, SE-221 00 Lund, SwedenPhosphorylation is a common post-translational modification among intrinsically disordered proteins and regions, which helps regulate function by changing the protein conformations, dynamics, and interactions with binding partners. To fully comprehend the effects of phosphorylation, computer simulations are a helpful tool, although they are dependent on the accuracy of the force field used. Here, we compared the conformational ensembles produced by Amber ff99SB-ILDN+TIP4P-D and CHARMM36m, for four phosphorylated disordered peptides ranging in length from 14–43 residues. CHARMM36m consistently produced more compact conformations with a higher content of bends, mainly due to more stable salt bridges. Based on comparisons with experimental size estimates for the shortest and longest peptide, CHARMM36m appeared to overestimate the compactness. The difference between the force fields was largest for the peptide showing the greatest separation between positively charged and phosphorylated residues, in line with the importance of charge distribution. For this peptide, the conformational ensemble did not change significantly upon increasing the ionic strength from 0 mM to 150 mM, despite a reduction of the salt-bridging probability in the CHARMM36m simulations, implying that salt concentration has negligible effects in this study.https://www.mdpi.com/1422-0067/22/18/10174intrinsically disordered proteinsphosphorylationforce fields
spellingShingle Ellen Rieloff
Marie Skepö
Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison
International Journal of Molecular Sciences
intrinsically disordered proteins
phosphorylation
force fields
title Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison
title_full Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison
title_fullStr Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison
title_full_unstemmed Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison
title_short Molecular Dynamics Simulations of Phosphorylated Intrinsically Disordered Proteins: A Force Field Comparison
title_sort molecular dynamics simulations of phosphorylated intrinsically disordered proteins a force field comparison
topic intrinsically disordered proteins
phosphorylation
force fields
url https://www.mdpi.com/1422-0067/22/18/10174
work_keys_str_mv AT ellenrieloff moleculardynamicssimulationsofphosphorylatedintrinsicallydisorderedproteinsaforcefieldcomparison
AT marieskepo moleculardynamicssimulationsofphosphorylatedintrinsicallydisorderedproteinsaforcefieldcomparison