Using Complementary NMR Data Sets To Detect Inconsistencies and Model Flaws in the Structure Determination of Human Interleukin-4

Smith, Lorna J.; Gunsteren, Wilfred F. van; Hansen, Niels

doi:10.1021/acs.jpcb.7b03647

Cited by 2 publications

(3 citation statements)

References 53 publications

(95 reference statements)

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“…3 J‐coupling can be related to a torsional angle through the Karplus relation. At particular angles, variations in the Karplus relation parameters (a, b, c) lead to differences of up to 3 Hz even though the experimental uncertainties are generally lower than 0.1 Hz …”

Section: Methodsmentioning

confidence: 99%

“…At particular angles, variations in the Karplus relation parameters (a, b, c) lead to differences of up to 3 Hz even though the experimental uncertainties are generally lower than 0.1 Hz. [57][58][59] 3 J HNHα , 3 J HαHβ , and 3 J HNH2 coupling constants are related to the dihedral angles of � S , c S and q NÀ Acetyl (Figure 2), and were calculated from MD and LEUS simulations using the following Karplus relations. [60][61][62] Note that for Thr there is one 3 J HαHβ , while for Ser there are two possible values.…”

Section: J-coupling Constants and Noe Calculationsmentioning

confidence: 99%

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Structural Aspects of the O‐glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments

et al. 2019

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A powerful conformational searching and enhanced sampling simulation method, and unbiased molecular dynamics simulations have been used along with NMR spectroscopic observables to provide a detailed structural view of O‐glycosylation. For four model systems, the force‐field parameters can accurately predict experimental NMR observables (J couplings and NOE's). This enables us to derive conclusions based on the generated ensembles, in which O‐glycosylation affects the peptide backbone conformation by forcing it towards to an extended conformation. An exception is described for β ‐GalNAc‐Thr where the α content is increased and stabilized via hydrogen bonding between the sugar and the peptide backbone, which was not observed in the rest of the studied systems. These observations might offer an explanation for the evolutionary preference of α ‐linked GalNAc glycosylation instead of a β link.

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Section: Methodsmentioning

confidence: 99%

Section: J-coupling Constants and Noe Calculationsmentioning

confidence: 99%

Structural Aspects of the O‐glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments

et al. 2019

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“…This suggests the use of S 2 order‐parameter structure refinement using time averaging in order to obtain a conformational ensemble compatible with the order‐parameter data. The technique of time‐averaging order‐parameter structure refinement has been tested on the backbone 15 N− 1 H order parameters of the B3 domain of protein G, [9] and subsequently applied to backbone 15 N− 1 H order parameters of the protein IL‐4 at pH 6 to detect inconsistencies and model flaws regarding complementary sets of NMR data, [18] and applied to backbone 15 N− 1 H order parameters of the protein hGH at pH 2.7 in order to explain the occurrence of low order‐parameter values in the middle of stable helices [19] …”

Section: Introductionmentioning

confidence: 99%

On the Use of Side‐Chain NMR Relaxation Data to Derive Structural and Dynamical Information on Proteins: A Case Study Using Hen Lysozyme

2020

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Values of S2CH and S2NH order parameters derived from NMR relaxation measurements on proteins cannot be used straightforwardly to determine protein structure because they cannot be related to a single protein structure, but are defined in terms of an average over a conformational ensemble. Molecular dynamics simulation can generate a conformational ensemble and thus can be used to restrain S2CH and S2NH order parameters towards experimentally derived target values S2CH (exp) and S2NH (exp). Application of S2CH and S2NH order‐parameter restraining MD simulation to bond vectors in 63 side chains of the protein hen egg white lysozyme using 51 S2CH (exp) target values and 28 S2NH (exp) target values shows that a conformational ensemble compatible with the experimentally derived data can be obtained by using this technique. It is observed that S2CH order‐parameter restraining of C−H bonds in methyl groups is less reliable than S2NH order‐parameter restraining because of the possibly less valid assumptions and approximations used to derive experimental S2CH (exp) values from NMR relaxation measurements and the necessity to adopt the assumption of uniform rotational motion of methyl C−H bonds around their symmetry axis and of the independence of these motions from each other. The restrained simulations demonstrate that side chains on the protein surface are highly dynamic. Any hydrogen bonds they form and that appear in any of four different crystal structures, are fluctuating with short lifetimes in solution.

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Using Complementary NMR Data Sets To Detect Inconsistencies and Model Flaws in the Structure Determination of Human Interleukin-4

Cited by 2 publications

References 53 publications

Structural Aspects of the O‐glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments

Structural Aspects of the O‐glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments

On the Use of Side‐Chain NMR Relaxation Data to Derive Structural and Dynamical Information on Proteins: A Case Study Using Hen Lysozyme

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