Molecular dynamics simulations of phosphorylated intrinsically disordered proteins : A force field comparison
(2021) In International Journal of Molecular Sciences 22(18).- Abstract
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 phospho-rylation, 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... (More)
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 phospho-rylation, 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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- author
- Rieloff, Ellen LU and Skepö, Marie LU
- organization
- publishing date
- 2021-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Force fields, Intrinsically disordered proteins, Phosphorylation
- in
- International Journal of Molecular Sciences
- volume
- 22
- issue
- 18
- article number
- 10174
- publisher
- MDPI AG
- external identifiers
-
- scopus:85115169132
- pmid:34576338
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms221810174
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: Funding: Financial support was given by the Royal Physiographic Society in Lund and the Bertil Andersson foundation. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
- id
- ad56b1e8-1c96-4b37-afcd-4bcc6c807426
- date added to LUP
- 2021-09-29 09:09:59
- date last changed
- 2024-04-20 11:59:39
@article{ad56b1e8-1c96-4b37-afcd-4bcc6c807426,
abstract = {{<p>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 phospho-rylation, 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.</p>}},
author = {{Rieloff, Ellen and Skepö, Marie}},
issn = {{1661-6596}},
keywords = {{Force fields; Intrinsically disordered proteins; Phosphorylation}},
language = {{eng}},
number = {{18}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{Molecular dynamics simulations of phosphorylated intrinsically disordered proteins : A force field comparison}},
url = {{http://dx.doi.org/10.3390/ijms221810174}},
doi = {{10.3390/ijms221810174}},
volume = {{22}},
year = {{2021}},
}