Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy

Schneider, Robert; Huang, Jie Rong; Yao, Mingxi; Communie, Guillaume; Ozenne, Valéry; Mollica, Luca; Salmon, Loïc; Jensen, Malene Ringkjøbing; Blackledge, Martin

doi:10.1039/c1mb05291h

Cited by 98 publications

(133 citation statements)

References 98 publications

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“…[134][135][136] By all this information combined, one can describe the structure of an IDP as an ensemble of conformations. To this end, two broad approaches have been developed: either through restrained molecular dynamics simulations, or the generation of a large number of conformations and selection of a subset that fits the data.…”

Section: Idps As Conformational Ensemblesmentioning

confidence: 99%

Introducing Protein Intrinsic Disorder

et al. 2014

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Section: Idps As Conformational Ensemblesmentioning

confidence: 99%

Introducing Protein Intrinsic Disorder

et al. 2014

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“…The software GAJOE, which is part of the software package EOM (Bernadό et al 2007;Bernadό and Svergun 2012), selects conformers based only on SAXS data by iteratively fitting theoretical scattering curves to experimentally determined ones. The software AS-TEROIDS (Salmon et al 2010;Schneider et al 2012) uses a genetic algorithm for selecting ensembles and iteratively repopulating the underlying potential energy landscapes by comparing theoretical parameters to available NMR and SAXS data. The algorithm converges to ensembles whose elements are unique, yet, on average, explain the experimental data equally well.…”

Section: Ensembles Selected From Random Poolsmentioning

confidence: 99%

The Protein Ensemble Database

Váradi

Tompa

2015

Advances in Experimental Medicine and Biology

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The scientific community's major conceptual notion of structural biology has recently shifted in emphasis from the classical structure-function paradigm due to the emergence of intrinsically disordered proteins (IDPs). As opposed to their folded cousins, these proteins are defined by the lack of a stable 3D fold and a high degree of inherent structural heterogeneity that is closely tied to their function. Due to their flexible nature, solution techniques such as small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) spectroscopy and fluorescence resonance energy transfer (FRET) are particularly well-suited for characterizing their biophysical properties. Computationally derived structural ensembles based on such experimental measurements provide models of the conformational sampling displayed by these proteins, and they may offer valuable insights into the functional consequences of inherent flexibility. The Protein Ensemble Database (http://pedb.vib.be) is the first openly accessible, manually curated online resource storing the ensemble models, protocols used during the calculation procedure, and underlying primary experimental data derived from SAXS and/or NMR measurements. By making this previously inaccessible data freely available to researchers, this novel resource is expected to promote the development of more advanced modelling methodologies, facilitate the design of standardized calculation protocols, and consequently lead to a better understanding of how function arises from the disordered state.

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“…In contrast, residual dipolar couplings (RDC) are more promising tools as they sample an angular dependence with respect to a common frame of reference. Let us consider the RDC associated with a 1 H-15 N pair: because of the orientation of the NH vector, this coupling will change sign in a transient helical element as compared with an unfolded chain (87).…”

Section: Figmentioning

confidence: 99%

An Introduction to Biological NMR Spectroscopy

Marion

2013

Molecular & Cellular Proteomics

161

118

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NMR spectroscopy is a powerful tool for biologists interested in the structure, dynamics, and interactions of biological macromolecules. This review aims at presenting in an accessible manner the requirements and limitations of this technique. As an introduction, the history of NMR will highlight how the method evolved from physics to chemistry and finally to biology over several decades. We then introduce the NMR spectral parameters used in structural biology, namely the chemical shift, the J-coupling, nuclear Overhauser effects, and residual dipolar couplings. Resonance assignment, the required step for any further NMR study, bears a resemblance to jigsaw puzzle strategy. The NMR spectral parameters are then converted into angle and distances and used as input using restrained molecular dynamics to compute a bundle of structures. When interpreting a NMR-derived structure, the biologist has to judge its quality on the basis of the statistics provided. When the 3D structure is a priori known by other means, the molecular interaction with a partner can be mapped by NMR: information on the binding interface as well as on kinetic and thermodynamic constants can be gathered. NMR is suitable to monitor, over a wide range of frequencies, protein fluctuations that play a crucial role in their biological function. In the last section of this review, intrinsically disordered proteins, which have escaped the attention of classical structural biology, are discussed in the perspective of NMR, one of the rare available techniques able to describe structural ensembles. This Tutorial is part of the International Proteomics

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Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy

Cited by 98 publications

References 98 publications

Introducing Protein Intrinsic Disorder

Introducing Protein Intrinsic Disorder

The Protein Ensemble Database

An Introduction to Biological NMR Spectroscopy

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