REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution.
Nuclear Magnetic Resonance (NMR) spectroscopy is one of the three primary experimental means of characterizing macromolecular structures, including protein structures. Structure determination by solution NMR spectroscopy has traditionally relied heavily on distance restraints derived from nuclear Ov...
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doaj-265bfc07251b492dbea97bc06c5745612021-06-24T04:31:01ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-02-01172e100806010.1371/journal.pcbi.1008060REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution.Casey A ColeNourhan S DaighamGaohua LiuGaetano T MontelioneHomayoun ValafarNuclear Magnetic Resonance (NMR) spectroscopy is one of the three primary experimental means of characterizing macromolecular structures, including protein structures. Structure determination by solution NMR spectroscopy has traditionally relied heavily on distance restraints derived from nuclear Overhauser effect (NOE) measurements. While structure determination of proteins from NOE-based restraints is well understood and broadly used, structure determination from Residual Dipolar Couplings (RDCs) is relatively less well developed. Here, we describe the new features of the protein structure modeling program REDCRAFT and focus on the new Adaptive Decimation (AD) feature. The AD plays a critical role in improving the robustness of REDCRAFT to missing or noisy data, while allowing structure determination of larger proteins from less data. In this report we demonstrate the successful application of REDCRAFT in structure determination of proteins ranging in size from 50 to 145 residues using experimentally collected data, and of larger proteins (145 to 573 residues) using simulated RDC data. In both cases, REDCRAFT uses only RDC data that can be collected from perdeuterated proteins. Finally, we compare the accuracy of structure determination from RDCs alone with traditional NOE-based methods for the structurally novel PF.2048.1 protein. The RDC-based structure of PF.2048.1 exhibited 1.0 Å BB-RMSD with respect to a high-quality NOE-based structure. Although optimal strategies would include using RDC data together with chemical shift, NOE, and other NMR data, these studies provide proof-of-principle for robust structure determination of largely-perdeuterated proteins from RDC data alone using REDCRAFT.https://doi.org/10.1371/journal.pcbi.1008060 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Casey A Cole Nourhan S Daigham Gaohua Liu Gaetano T Montelione Homayoun Valafar |
spellingShingle |
Casey A Cole Nourhan S Daigham Gaohua Liu Gaetano T Montelione Homayoun Valafar REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution. PLoS Computational Biology |
author_facet |
Casey A Cole Nourhan S Daigham Gaohua Liu Gaetano T Montelione Homayoun Valafar |
author_sort |
Casey A Cole |
title |
REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution. |
title_short |
REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution. |
title_full |
REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution. |
title_fullStr |
REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution. |
title_full_unstemmed |
REDCRAFT: A computational platform using residual dipolar coupling NMR data for determining structures of perdeuterated proteins in solution. |
title_sort |
redcraft: a computational platform using residual dipolar coupling nmr data for determining structures of perdeuterated proteins in solution. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Computational Biology |
issn |
1553-734X 1553-7358 |
publishDate |
2021-02-01 |
description |
Nuclear Magnetic Resonance (NMR) spectroscopy is one of the three primary experimental means of characterizing macromolecular structures, including protein structures. Structure determination by solution NMR spectroscopy has traditionally relied heavily on distance restraints derived from nuclear Overhauser effect (NOE) measurements. While structure determination of proteins from NOE-based restraints is well understood and broadly used, structure determination from Residual Dipolar Couplings (RDCs) is relatively less well developed. Here, we describe the new features of the protein structure modeling program REDCRAFT and focus on the new Adaptive Decimation (AD) feature. The AD plays a critical role in improving the robustness of REDCRAFT to missing or noisy data, while allowing structure determination of larger proteins from less data. In this report we demonstrate the successful application of REDCRAFT in structure determination of proteins ranging in size from 50 to 145 residues using experimentally collected data, and of larger proteins (145 to 573 residues) using simulated RDC data. In both cases, REDCRAFT uses only RDC data that can be collected from perdeuterated proteins. Finally, we compare the accuracy of structure determination from RDCs alone with traditional NOE-based methods for the structurally novel PF.2048.1 protein. The RDC-based structure of PF.2048.1 exhibited 1.0 Å BB-RMSD with respect to a high-quality NOE-based structure. Although optimal strategies would include using RDC data together with chemical shift, NOE, and other NMR data, these studies provide proof-of-principle for robust structure determination of largely-perdeuterated proteins from RDC data alone using REDCRAFT. |
url |
https://doi.org/10.1371/journal.pcbi.1008060 |
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