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Self-Diffusive Properties of the Intrinsically Disordered Protein Histatin 5 and the Impact of Crowding Thereon : A Combined Neutron Spectroscopy and Molecular Dynamics Simulation Study

Fagerberg, Eric LU ; Lenton, Samuel LU ; Nylander, Tommy LU ; Seydel, Tilo and Skepö, Marie LU (2021) In Journal of Physical Chemistry B
Abstract

Intrinsically disordered proteins (IDPs) are proteins that, in comparison with globular/structured proteins, lack a distinct tertiary structure. Here, we use the model IDP, Histatin 5, for studying its dynamical properties under self-crowding conditions with quasi-elastic neutron scattering in combination with full atomistic molecular dynamics (MD) simulations. The aim is to determine the effects of crowding on the center-of-mass diffusion as well as the internal diffusive behavior. The diffusion was found to decrease significantly, which we hypothesize can be attributed to some degree of aggregation at higher protein concentrations, (≥100 mg/mL), as indicated by recent small-angle X-ray scattering studies. Temperature effects are also... (More)

Intrinsically disordered proteins (IDPs) are proteins that, in comparison with globular/structured proteins, lack a distinct tertiary structure. Here, we use the model IDP, Histatin 5, for studying its dynamical properties under self-crowding conditions with quasi-elastic neutron scattering in combination with full atomistic molecular dynamics (MD) simulations. The aim is to determine the effects of crowding on the center-of-mass diffusion as well as the internal diffusive behavior. The diffusion was found to decrease significantly, which we hypothesize can be attributed to some degree of aggregation at higher protein concentrations, (≥100 mg/mL), as indicated by recent small-angle X-ray scattering studies. Temperature effects are also considered and found to, largely, follow Stokes-Einstein behavior. Simple geometric considerations fail to accurately predict the rates of diffusion, while simulations show semiquantitative agreement with experiments, dependent on assumptions of the ratio between translational and rotational diffusion. A scaling law that previously was found to successfully describe the behavior of globular proteins was found to be inadequate for the IDP, Histatin 5. Analysis of the MD simulations show that the width of the distribution with respect to diffusion is not a simplistic mirroring of the distribution of radius of gyration, hence, displaying the particular features of IDPs that need to be accounted for.

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Contribution to journal
publication status
published
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in
Journal of Physical Chemistry B
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85123846200
  • pmid:35044776
ISSN
1520-6106
DOI
10.1021/acs.jpcb.1c08976
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 The Authors. Published by American Chemical Society.
id
620a0467-d59c-4c10-a7cb-fd2465c2113d
date added to LUP
2022-02-16 15:59:29
date last changed
2024-06-14 13:45:26
@article{620a0467-d59c-4c10-a7cb-fd2465c2113d,
  abstract     = {{<p>Intrinsically disordered proteins (IDPs) are proteins that, in comparison with globular/structured proteins, lack a distinct tertiary structure. Here, we use the model IDP, Histatin 5, for studying its dynamical properties under self-crowding conditions with quasi-elastic neutron scattering in combination with full atomistic molecular dynamics (MD) simulations. The aim is to determine the effects of crowding on the center-of-mass diffusion as well as the internal diffusive behavior. The diffusion was found to decrease significantly, which we hypothesize can be attributed to some degree of aggregation at higher protein concentrations, (≥100 mg/mL), as indicated by recent small-angle X-ray scattering studies. Temperature effects are also considered and found to, largely, follow Stokes-Einstein behavior. Simple geometric considerations fail to accurately predict the rates of diffusion, while simulations show semiquantitative agreement with experiments, dependent on assumptions of the ratio between translational and rotational diffusion. A scaling law that previously was found to successfully describe the behavior of globular proteins was found to be inadequate for the IDP, Histatin 5. Analysis of the MD simulations show that the width of the distribution with respect to diffusion is not a simplistic mirroring of the distribution of radius of gyration, hence, displaying the particular features of IDPs that need to be accounted for.</p>}},
  author       = {{Fagerberg, Eric and Lenton, Samuel and Nylander, Tommy and Seydel, Tilo and Skepö, Marie}},
  issn         = {{1520-6106}},
  language     = {{eng}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Physical Chemistry B}},
  title        = {{Self-Diffusive Properties of the Intrinsically Disordered Protein Histatin 5 and the Impact of Crowding Thereon : A Combined Neutron Spectroscopy and Molecular Dynamics Simulation Study}},
  url          = {{http://dx.doi.org/10.1021/acs.jpcb.1c08976}},
  doi          = {{10.1021/acs.jpcb.1c08976}},
  year         = {{2021}},
}