On the Calculation of SAXS Profiles of Folded and Intrinsically Disordered Proteins from Computer Simulations
(2018) In Journal of Molecular Biology 430(16). p.2521-2539- Abstract
Solution techniques such as small-angle X-ray scattering (SAXS) play a central role in structural studies of intrinsically disordered proteins (IDPs); yet, due to low resolution, it is generally necessary to combine SAXS with additional experimental sources of data and to use molecular simulations. Computational methods for the calculation of theoretical SAXS intensity profiles can be separated into two groups, depending on whether the solvent is modeled implicitly as continuous electron density or considered explicitly. The former offers reduced computational cost but requires the definition of a number of free parameters to account for, for example, the excess density of the solvation layer. Overfitting can thus be an issue,... (More)
Solution techniques such as small-angle X-ray scattering (SAXS) play a central role in structural studies of intrinsically disordered proteins (IDPs); yet, due to low resolution, it is generally necessary to combine SAXS with additional experimental sources of data and to use molecular simulations. Computational methods for the calculation of theoretical SAXS intensity profiles can be separated into two groups, depending on whether the solvent is modeled implicitly as continuous electron density or considered explicitly. The former offers reduced computational cost but requires the definition of a number of free parameters to account for, for example, the excess density of the solvation layer. Overfitting can thus be an issue, particularly when the structural ensemble is unknown. Here, we investigate and show how small variations of the contrast of the hydration shell, δρ, severely affect the outcome, analysis and interpretation of computed SAXS profiles for folded and disordered proteins. For both the folded and disordered proteins studied here, using a default δρ may, in some cases, result in the calculation of non-representative SAXS profiles, leading to an overestimation of their size and a misinterpretation of their structural nature. The solvation layer of the different IDP simulations also impacts their size estimates differently, depending on the protein force field used. The same is not true for the folded protein simulations, suggesting differences in the solvation of the two classes of proteins, and indicating that different force fields optimized for IDPs may cause expansion of the polypeptide chain through different physical mechanisms.
(Less)
- author
- Henriques, João LU ; Arleth, Lise ; Lindorff-Larsen, Kresten and Skepö, Marie LU
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- conformational ensemble, hydration shell, intrinsically disordered protein, molecular dynamics, SAXS
- in
- Journal of Molecular Biology
- volume
- 430
- issue
- 16
- pages
- 2521 - 2539
- publisher
- Elsevier
- external identifiers
-
- pmid:29548755
- scopus:85044319160
- ISSN
- 0022-2836
- DOI
- 10.1016/j.jmb.2018.03.002
- language
- English
- LU publication?
- yes
- id
- 8a8ea947-6064-4561-a106-ec8ec94e5661
- date added to LUP
- 2018-04-10 07:31:24
- date last changed
- 2024-05-27 09:55:33
@article{8a8ea947-6064-4561-a106-ec8ec94e5661,
abstract = {{<p>Solution techniques such as small-angle X-ray scattering (SAXS) play a central role in structural studies of intrinsically disordered proteins (IDPs); yet, due to low resolution, it is generally necessary to combine SAXS with additional experimental sources of data and to use molecular simulations. Computational methods for the calculation of theoretical SAXS intensity profiles can be separated into two groups, depending on whether the solvent is modeled implicitly as continuous electron density or considered explicitly. The former offers reduced computational cost but requires the definition of a number of free parameters to account for, for example, the excess density of the solvation layer. Overfitting can thus be an issue, particularly when the structural ensemble is unknown. Here, we investigate and show how small variations of the contrast of the hydration shell, δρ, severely affect the outcome, analysis and interpretation of computed SAXS profiles for folded and disordered proteins. For both the folded and disordered proteins studied here, using a default δρ may, in some cases, result in the calculation of non-representative SAXS profiles, leading to an overestimation of their size and a misinterpretation of their structural nature. The solvation layer of the different IDP simulations also impacts their size estimates differently, depending on the protein force field used. The same is not true for the folded protein simulations, suggesting differences in the solvation of the two classes of proteins, and indicating that different force fields optimized for IDPs may cause expansion of the polypeptide chain through different physical mechanisms.</p>}},
author = {{Henriques, João and Arleth, Lise and Lindorff-Larsen, Kresten and Skepö, Marie}},
issn = {{0022-2836}},
keywords = {{conformational ensemble; hydration shell; intrinsically disordered protein; molecular dynamics; SAXS}},
language = {{eng}},
number = {{16}},
pages = {{2521--2539}},
publisher = {{Elsevier}},
series = {{Journal of Molecular Biology}},
title = {{On the Calculation of SAXS Profiles of Folded and Intrinsically Disordered Proteins from Computer Simulations}},
url = {{http://dx.doi.org/10.1016/j.jmb.2018.03.002}},
doi = {{10.1016/j.jmb.2018.03.002}},
volume = {{430}},
year = {{2018}},
}