An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling
Paramagnetic nuclear magnetic resonance (NMR) methods have emerged as powerful tools for structure determination of large, sparsely protonated proteins. However traditional applications face several challenges, including a need for large datasets to offset the sparsity of restraints, the difficulty...
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doaj-211d2c57e1a4445eaaf71c1468c36b142021-08-12T07:52:24ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-08-01810.3389/fmolb.2021.676268676268An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical ModelingKari Gaalswyk0Zhihong Liu1Hans J. Vogel2Justin L. MacCallum3Department of Chemistry, University of Calgary, Calgary, AB, CanadaDepartment of Biological Sciences, University of Calgary, Calgary, AB, CanadaDepartment of Biological Sciences, University of Calgary, Calgary, AB, CanadaDepartment of Chemistry, University of Calgary, Calgary, AB, CanadaParamagnetic nuclear magnetic resonance (NMR) methods have emerged as powerful tools for structure determination of large, sparsely protonated proteins. However traditional applications face several challenges, including a need for large datasets to offset the sparsity of restraints, the difficulty in accounting for the conformational heterogeneity of the spin-label, and noisy experimental data. Here we propose an integrative approach to structure determination combining sparse paramagnetic NMR with physical modelling to infer approximate protein structural ensembles. We use calmodulin in complex with the smooth muscle myosin light chain kinase peptide as a model system. Despite acquiring data from samples labeled only at the backbone amide positions, we are able to produce an ensemble with an average RMSD of ∼2.8 Å from a reference X-ray crystal structure. Our approach requires only backbone chemical shifts and measurements of the paramagnetic relaxation enhancement and residual dipolar couplings that can be obtained from sparsely labeled samples.https://www.frontiersin.org/articles/10.3389/fmolb.2021.676268/fullparamagnetic relaxation enhancementNMRmodelingprotein structureintegrative structural biologycalmodulin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kari Gaalswyk Zhihong Liu Hans J. Vogel Justin L. MacCallum |
spellingShingle |
Kari Gaalswyk Zhihong Liu Hans J. Vogel Justin L. MacCallum An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling Frontiers in Molecular Biosciences paramagnetic relaxation enhancement NMR modeling protein structure integrative structural biology calmodulin |
author_facet |
Kari Gaalswyk Zhihong Liu Hans J. Vogel Justin L. MacCallum |
author_sort |
Kari Gaalswyk |
title |
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling |
title_short |
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling |
title_full |
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling |
title_fullStr |
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling |
title_full_unstemmed |
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling |
title_sort |
integrative approach to determine 3d protein structures using sparse paramagnetic nmr data and physical modeling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2021-08-01 |
description |
Paramagnetic nuclear magnetic resonance (NMR) methods have emerged as powerful tools for structure determination of large, sparsely protonated proteins. However traditional applications face several challenges, including a need for large datasets to offset the sparsity of restraints, the difficulty in accounting for the conformational heterogeneity of the spin-label, and noisy experimental data. Here we propose an integrative approach to structure determination combining sparse paramagnetic NMR with physical modelling to infer approximate protein structural ensembles. We use calmodulin in complex with the smooth muscle myosin light chain kinase peptide as a model system. Despite acquiring data from samples labeled only at the backbone amide positions, we are able to produce an ensemble with an average RMSD of ∼2.8 Å from a reference X-ray crystal structure. Our approach requires only backbone chemical shifts and measurements of the paramagnetic relaxation enhancement and residual dipolar couplings that can be obtained from sparsely labeled samples. |
topic |
paramagnetic relaxation enhancement NMR modeling protein structure integrative structural biology calmodulin |
url |
https://www.frontiersin.org/articles/10.3389/fmolb.2021.676268/full |
work_keys_str_mv |
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