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...
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MDPI AG
2021-09-01
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Online Access: | https://www.mdpi.com/1422-0067/22/18/10174 |
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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. |
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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 |
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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 |