Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins
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Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins. / Pesce, Francesco; Newcombe, Estella A.; Seiffert, Pernille; Tranchant, Emil E.; Olsen, Johan G.; Grace, Christy R.; Kragelund, Birthe B.; Lindorff-Larsen, Kresten.
In: Biophysical Journal, Vol. 122, No. 2, 2023, p. 310-321.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins
AU - Pesce, Francesco
AU - Newcombe, Estella A.
AU - Seiffert, Pernille
AU - Tranchant, Emil E.
AU - Olsen, Johan G.
AU - Grace, Christy R.
AU - Kragelund, Birthe B.
AU - Lindorff-Larsen, Kresten
N1 - Publisher Copyright: © 2022 Biophysical Society
PY - 2023
Y1 - 2023
N2 - Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins, which contains information about the overall dimension of a protein in solution. The comparison of this value with structural models of intrinsically disordered proteins is nonetheless impaired by the uncertainty of the accuracy of the methods for computing the hydrodynamic radius from atomic coordinates. To tackle this issue, we here build conformational ensembles of 11 intrinsically disordered proteins that we ensure are in agreement with measurements of compaction by small-angle x-ray scattering. We then use these ensembles to identify the forward model that more closely fits the radii derived from pulsed-field gradient NMR diffusion experiments. Of the models we examined, we find that the Kirkwood-Riseman equation provides the best description of the hydrodynamic radius probed by pulsed-field gradient NMR experiments. While some minor discrepancies remain, our results enable better use of measurements of the hydrodynamic radius in integrative modeling and for force field benchmarking and parameterization.
AB - Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins, which contains information about the overall dimension of a protein in solution. The comparison of this value with structural models of intrinsically disordered proteins is nonetheless impaired by the uncertainty of the accuracy of the methods for computing the hydrodynamic radius from atomic coordinates. To tackle this issue, we here build conformational ensembles of 11 intrinsically disordered proteins that we ensure are in agreement with measurements of compaction by small-angle x-ray scattering. We then use these ensembles to identify the forward model that more closely fits the radii derived from pulsed-field gradient NMR diffusion experiments. Of the models we examined, we find that the Kirkwood-Riseman equation provides the best description of the hydrodynamic radius probed by pulsed-field gradient NMR experiments. While some minor discrepancies remain, our results enable better use of measurements of the hydrodynamic radius in integrative modeling and for force field benchmarking and parameterization.
U2 - 10.1016/j.bpj.2022.12.013
DO - 10.1016/j.bpj.2022.12.013
M3 - Journal article
C2 - 36518077
AN - SCOPUS:85144936282
VL - 122
SP - 310
EP - 321
JO - Biophysical Society. Annual Meeting. Abstracts
JF - Biophysical Society. Annual Meeting. Abstracts
SN - 0523-6800
IS - 2
ER -
ID: 334258559