Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Dokumenter

  • Preprint

    Indsendt manuskript, 1,97 MB, PDF-dokument

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.
OriginalsprogEngelsk
TidsskriftBiophysical Journal
Vol/bind122
Udgave nummer2
Sider (fra-til)310-321
Antal sider12
ISSN0006-3495
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We thank our colleagues who measured the data that have made this work possible. We acknowledge the use of computational resources from the core facility for biocomputing at the Department of Biology and support for NMR infrastructure from Villumfonden. We thank the beamline scientists Cy Jeffries at EMBL DESY P12 and Nathan Cowieson at DIAMOND B21 for technical support and data acquisition, and Jacob H. Martinsen for assistance with protein purification and Eric M. Morrow and Stine F. Pedersen for input on NHE6cmdd. We thank Amanda D. Due for preparation of the ANAC046 samples. We thank Anne Bremer and Tanja Mittag for support and assistance in purification and studies of the A1 LCD, and acknowledge access to the St. Jude Biomolecular NMR Spectroscopy Center. We thank Giulio Tesei for fruitful discussion on how to calculate the Kirkwood-Riseman equation. We thank David de Sancho for comments on our work. This research was supported by the Lundbeck Foundation BRAINSTRUC initiative (R155-2015-2666 to B.K.K. and K.L.-L.) and the Novo Nordisk Foundation Challenge grant REPIN (no. NNF18OC0033926 to B.B.K.). E.A.N. has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 101023654. The authors declare no competing interests.

Funding Information:
We thank our colleagues who measured the data that have made this work possible. We acknowledge the use of computational resources from the core facility for biocomputing at the Department of Biology and support for NMR infrastructure from Villumfonden. We thank the beamline scientists Cy Jeffries at EMBL DESY P12 and Nathan Cowieson at DIAMOND B21 for technical support and data acquisition, and Jacob H. Martinsen for assistance with protein purification and Eric M. Morrow and Stine F. Pedersen for input on NHE6cmdd. We thank Amanda D. Due for preparation of the ANAC046 samples. We thank Anne Bremer and Tanja Mittag for support and assistance in purification and studies of the A1 LCD, and acknowledge access to the St. Jude Biomolecular NMR Spectroscopy Center. We thank Giulio Tesei for fruitful discussion on how to calculate the Kirkwood-Riseman equation. We thank David de Sancho for comments on our work. This research was supported by the Lundbeck Foundation BRAINSTRUC initiative ( R155-2015-2666 to B.K.K. and K.L.-L.) and the Novo Nordisk Foundation Challenge grant REPIN (no. NNF18OC0033926 to B.B.K.). E.A.N. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 101023654 .

Publisher Copyright:
© 2022 Biophysical Society

Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk


Ingen data tilgængelig

ID: 334258559