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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Main Authors: Casey A Cole, Nourhan S Daigham, Gaohua Liu, Gaetano T Montelione, Homayoun Valafar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-02-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1008060
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spelling 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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