Rapid Protein Global Fold Determination Using Ultrasparse Sampling, High-Dynamic Range Artifact Suppression, and Time-Shared NOESY.
Saved in:
| Title: | Rapid Protein Global Fold Determination Using Ultrasparse Sampling, High-Dynamic Range Artifact Suppression, and Time-Shared NOESY. |
|---|---|
| Authors: | Coggins, Brian E.1 brian.coggins@duke.edu, Werner-Allen, Jonathan W.1, Yan, Anthony1, Pei Zhou1 peizhou@biochem.duke.edu |
| Source: | Journal of the American Chemical Society. 11/14/2012, Vol. 134 Issue 45, p18619-18630. 12p. |
| Subjects: | Protein structure, Statistical sampling software, Protein folding -- Computer simulation, Four-manifolds (Topology), Proton transfer reactions |
| Abstract: | In structural studies of large proteins by NMR, global fold determination plays an increasingly important role in providing a first look at a target's topology and reducing assignment ambiguity in NOESY spectra of fully protonated samples. In this work, we demonstrate the use of ultrasparse sampling, a new data processing algorithm, and a 4-D time-shared NOESY experiment (1) to collect all NOEs in ²H/13C/15N-labeled protein samples with selectively protonated amide and ILV methyl groups at high resolution in only four days, and (2) to calculate global folds from this data using fully automated resonance assignment. The new algorithm, SCRUB, incorporates the CLEAN method for iterative artifact removal but applies an additional level of iteration, permitting real signals to be distinguished from noise and allowing nearly all artifacts generated by real signals to be eliminated. In simulations with 1.2% of the data required by Nyquist sampling, SCRUB achieves a dynamic range over 10000:1 (250× better artifact suppression than CLEAN) and completely quantitative reproduction of signal intensities, volumes, and line shapes. Applied to 4-D time-shared NOESY data, SCRUB processing dramatically reduces aliasing noise from strong diagonal signals, enabling the identification of weak NOE crosspeaks with intensities 100× less than those of diagonal signals. Nearly all of the expected peaks for interproton distances under 5 Å were observed. The practical benefit of this method is demonstrated with structure calculations for 23 kDa and 29 kDa test proteins using the automated assignment protocol of CYANA, in which unassigned 4-D time-shared NOESY peak lists produce accurate and well-converged global fold ensembles, whereas 3-D peak lists either fail to converge or produce significantly less accurate folds. The approach presented here succeeds with an order of magnitude less sampling than required by alternative methods for processing sparse 4-D data. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of the American Chemical Society is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: egs DbLabel: Engineering Source An: 83526354 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Rapid Protein Global Fold Determination Using Ultrasparse Sampling, High-Dynamic Range Artifact Suppression, and Time-Shared NOESY. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Coggins%2C+Brian+E%2E%22">Coggins, Brian E.</searchLink><relatesTo>1</relatesTo><i> brian.coggins@duke.edu</i><br /><searchLink fieldCode="AR" term="%22Werner-Allen%2C+Jonathan+W%2E%22">Werner-Allen, Jonathan W.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Yan%2C+Anthony%22">Yan, Anthony</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Pei+Zhou%22">Pei Zhou</searchLink><relatesTo>1</relatesTo><i> peizhou@biochem.duke.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+the+American+Chemical+Society%22">Journal of the American Chemical Society</searchLink>. 11/14/2012, Vol. 134 Issue 45, p18619-18630. 12p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Protein+structure%22">Protein structure</searchLink><br /><searchLink fieldCode="DE" term="%22Statistical+sampling+software%22">Statistical sampling software</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+folding+--+Computer+simulation%22">Protein folding -- Computer simulation</searchLink><br /><searchLink fieldCode="DE" term="%22Four-manifolds+%28Topology%29%22">Four-manifolds (Topology)</searchLink><br /><searchLink fieldCode="DE" term="%22Proton+transfer+reactions%22">Proton transfer reactions</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: In structural studies of large proteins by NMR, global fold determination plays an increasingly important role in providing a first look at a target's topology and reducing assignment ambiguity in NOESY spectra of fully protonated samples. In this work, we demonstrate the use of ultrasparse sampling, a new data processing algorithm, and a 4-D time-shared NOESY experiment (1) to collect all NOEs in ²H/13C/15N-labeled protein samples with selectively protonated amide and ILV methyl groups at high resolution in only four days, and (2) to calculate global folds from this data using fully automated resonance assignment. The new algorithm, SCRUB, incorporates the CLEAN method for iterative artifact removal but applies an additional level of iteration, permitting real signals to be distinguished from noise and allowing nearly all artifacts generated by real signals to be eliminated. In simulations with 1.2% of the data required by Nyquist sampling, SCRUB achieves a dynamic range over 10000:1 (250× better artifact suppression than CLEAN) and completely quantitative reproduction of signal intensities, volumes, and line shapes. Applied to 4-D time-shared NOESY data, SCRUB processing dramatically reduces aliasing noise from strong diagonal signals, enabling the identification of weak NOE crosspeaks with intensities 100× less than those of diagonal signals. Nearly all of the expected peaks for interproton distances under 5 Å were observed. The practical benefit of this method is demonstrated with structure calculations for 23 kDa and 29 kDa test proteins using the automated assignment protocol of CYANA, in which unassigned 4-D time-shared NOESY peak lists produce accurate and well-converged global fold ensembles, whereas 3-D peak lists either fail to converge or produce significantly less accurate folds. The approach presented here succeeds with an order of magnitude less sampling than required by alternative methods for processing sparse 4-D data. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of the American Chemical Society is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=83526354 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1021/ja307445y Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 18619 Subjects: – SubjectFull: Protein structure Type: general – SubjectFull: Statistical sampling software Type: general – SubjectFull: Protein folding -- Computer simulation Type: general – SubjectFull: Four-manifolds (Topology) Type: general – SubjectFull: Proton transfer reactions Type: general Titles: – TitleFull: Rapid Protein Global Fold Determination Using Ultrasparse Sampling, High-Dynamic Range Artifact Suppression, and Time-Shared NOESY. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Coggins, Brian E. – PersonEntity: Name: NameFull: Werner-Allen, Jonathan W. – PersonEntity: Name: NameFull: Yan, Anthony – PersonEntity: Name: NameFull: Pei Zhou IsPartOfRelationships: – BibEntity: Dates: – D: 14 M: 11 Text: 11/14/2012 Type: published Y: 2012 Identifiers: – Type: issn-print Value: 00027863 Numbering: – Type: volume Value: 134 – Type: issue Value: 45 Titles: – TitleFull: Journal of the American Chemical Society Type: main |
| ResultId | 1 |
