Hybrid Approaches to Structural Characterization of Conformational Ensembles of Complex Macromolecular Systems Combining NMR Residual Dipolar Couplings and Solution X-ray Scattering

Venditti, Vincenzo; Egner, Timothy K.; Clore, G. Marius

doi:10.1021/acs.chemrev.5b00592

Cited by 45 publications

(46 citation statements)

References 178 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More advanced approaches to restraint-based structure determination incorporate fitting to data derived from a combination of complementary techniques. For example, the combination of restraints obtained from NMR and SAXS experiments provides an established and powerful strategy for investigating structure and dynamics in large, multidomain proteins (139). Further, scoring functions based on a variety of proteomics data can be applied as an acceptance criterion to select computationally derived structures that satisfy experimentally determined spatial restraints; such an approach was employed to determine the molecular architecture of the yeast nuclear pore complex (6, 7).…”

Section: Computational Structural Refinement Methodsmentioning

confidence: 99%

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes

Goh

Hadden

Bernardi

et al. 2016

Annu. Rev. Biophys.

View full text Add to dashboard Cite

The rise of the computer as a powerful tool for model building and refinement has revolutionized the field of structure determination for large biomolecular systems. Despite the wide availability of robust experimental methods capable of resolving structural details across a range of spatiotemporal resolutions, computational hybrid methods have the unique ability to integrate the diverse data from multimodal techniques such as X-ray crystallography and electron microscopy into consistent, fully atomistic structures. Here, commonly employed strategies for computational real-space structural refinement are reviewed, and their specific applications are illustrated for several large macromolecular complexes: ribosome, virus capsids, chemosensory array, and photosynthetic chromatophore. The increasingly important role of computational methods in large-scale structural refinement, along with current and future challenges, is discussed.

show abstract

Section: Computational Structural Refinement Methodsmentioning

confidence: 99%

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes

Goh

Hadden

Bernardi

et al. 2016

Annu. Rev. Biophys.

View full text Add to dashboard Cite

show abstract

“…Specifically, SAS experimental data serve as a source of spatial restraints reflecting the overall dimensions and shape of the macromolecule, whereas NMR experimental data provide information regarding proximity of different parts of the biopolymer chain with respect to one another. Combined NMR-SAS structure determinations typically yield significant improvements in both accuracy and precision of structural models versus those computed solely with NMR data, particularly for dynamic systems [53, 54]. …”

Section: Future Of Structural Biology and The Role Of The Wwpdbmentioning

confidence: 99%

Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive

Burley

Berman

Kleywegt

et al. 2017

Methods in Molecular Biology

749

496

View full text Add to dashboard Cite

The Protein Data Bank (PDB)—the single global repository of experimentally determined 3D structures of biological macromolecules and their complexes—was established in 1971, becoming the first open-access digital resource in the biological sciences. The PDB archive currently houses ~130,000 entries (May 2017). It is managed by the Worldwide Protein Data Bank organization (wwPDB; wwpdb.org), which includes the RCSB Protein Data Bank (RCSB PDB; rcsb.org), the Protein Data Bank Japan (PDBj; pdbj.org), the Protein Data Bank in Europe (PDBe; pdbe.org), and BioMagResBank (BMRB; www.bmrb.wisc.edu). The four wwPDB partners operate a unified global software system that enforces community-agreed data standards and supports data Deposition, Biocuration, and Validation of ~11,000 new PDB entries annually (deposit.wwpdb.org). The RCSB PDB currently acts as the archive keeper, ensuring disaster recovery of PDB data and coordinating weekly updates. wwPDB partners disseminate the same archival data from multiple FTP sites, while operating complementary websites that provide their own views of PDB data with selected value-added information and links to related data resources. At present, the PDB archives experimental data, associated metadata, and 3D-atomic level structural models derived from three well-established methods: crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (3DEM). wwPDB partners are working closely with experts in related experimental areas (small-angle scattering, chemical cross-linking/mass spectrometry, Forster energy resonance transfer or FRET, etc.) to establish a federation of data resources that will support sustainable archiving and validation of 3D structural models and experimental data derived from integrative or hybrid methods.

show abstract

“…Obtaining as detailed as possible a picture of the disordered ensemble would ideally combine information from all of these experiments, if available. This can be done most comprehensively via an explicit ensemble description of the disordered state, either by reweighting of an existing molecular simulation [2][3][4][12][13][14][15][16][17] , or by performing an ensemble structural refinement with a very large number of replicas of the system [18][19][20][21][22][23] . However, a simpler approach is frequently useful.…”

Section: Introductionmentioning

confidence: 99%

Inferring Properties of Disordered Chains From FRET Transfer Efficiencies

Zheng

Zerze

Borgia

et al. 2018

Biophysical Journal

View full text Add to dashboard Cite

Förster resonance energy transfer (FRET) is a powerful tool for elucidating both structural and dynamic properties of unfolded or disordered biomolecules, especially in single-molecule experiments. However, the key observables, namely, the mean transfer efficiency and fluorescence lifetimes of the donor and acceptor chromophores, are averaged over a broad distribution of donor-acceptor distances. The inferred average properties of the ensemble therefore depend on the form of the model distribution chosen to describe the distance, as has been widely recognized. In addition, while the distribution for one type of polymer model may be appropriate for a chain under a given set of physico-chemical conditions, it may not be suitable for the same chain in a different environment so that even an apparently consistent application of the same model over all conditions may distort the apparent changes in chain dimensions with variation of temperature or solution composition. Here, we present an alternative and straightforward approach to determining ensemble properties from FRET data, in which the polymer scaling exponent is allowed to vary with solution conditions. In its simplest form, it requires either the mean FRET efficiency or fluorescence lifetime information. In order to test the accuracy of the method, we have utilized both synthetic FRET data from implicit and explicit solvent simulations for 30 different protein sequences, and experimental single-molecule FRET data for an intrinsically disordered and a denatured protein. In all cases, we find that the inferred radii of gyration are within 10% of the true values, thus providing higher accuracy than simpler polymer models. In addition, the scaling exponents obtained by our procedure are in good agreement with those determined directly from the molecular ensemble. Our approach can in principle be generalized to treating other ensemble-averaged functions of intramolecular distances from experimental data. Förster resonance energy transfer (FRET) is a powerful tool for elucidating both structural and dynamic properties of unfolded or disordered biomolecules, especially in single-molecule experiments. However, the key observables, namely the mean transfer efficiency and fluorescence lifetimes of the donor and acceptor chromophores, are averaged over a broad distribution of donor-acceptor distances. The inferred average properties of the ensemble therefore depend on the form of the model distribution chosen to describe the distance, as has been widely recognized. In addition, while the distribution for one type of polymer model may be appropriate for a chain under a given set of physico-chemical conditions, it may not be suitable for the same chain in a different environment, so that even an apparently consistent application of the same model over all conditions may distort the apparent changes in chain dimensions with variation of temperature or solution composition. Here, we present an alternative and straightforward approach to determining ensemble proper...

show abstract

Hybrid Approaches to Structural Characterization of Conformational Ensembles of Complex Macromolecular Systems Combining NMR Residual Dipolar Couplings and Solution X-ray Scattering

Cited by 45 publications

References 178 publications

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes

Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive

Inferring Properties of Disordered Chains From FRET Transfer Efficiencies

Contact Info

Product

Resources

About