Automated combined assignment of NOESY spectra and three-dimensional protein structure determination

Christian Mumenthaler, Peter Güntert, Werner Braun, Kurt Wüthrich

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed simultaneously. The input consists of a list of NOESY peak positions and a list of chemical shifts as obtained from sequence-specific resonance assignment. For the present applications of this approach the previously introduced NOAH routine was implemented in the distance geometry program DIANA. As an illustration, experimental 2D and 3D NOESY cross-peak lists of six proteins have been analyzed, for which complete sequence-specific 1H assignments are available for the polypeptide backbone and the amino acid side chains. The automated method assigned 70-90% of all NOESY cross peaks, which is on average 10% less than with the interactive approach, and only between 0.8% and 2.4% of the automatically assigned peaks had a different assignment than in the corresponding manually assigned peak lists. The structures obtained with NOAH/DIANA are in close agreement with those from manually assigned peak lists, and with both approaches the residual constraint violations correspond to high-quality NMR structure determinations. Systematic comparisons of the bundles of conformers that represent corresponding automatically and interactively determined structures document the absence of significant bias in either approach, indicating that an important step has been made towards automation of structure determination from NMR spectra.

Original languageEnglish (US)
Pages (from-to)351-362
Number of pages12
JournalJournal of Biomolecular NMR
Volume10
Issue number4
StatePublished - 1997

Fingerprint

Nuclear magnetic resonance
Chemical shift
Proteins
Automation
Amino Acids
Peptides
Geometry

Keywords

  • Error-tolerant target function
  • NOESY assignment
  • Protein structure determination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Spectroscopy

Cite this

Automated combined assignment of NOESY spectra and three-dimensional protein structure determination. / Mumenthaler, Christian; Güntert, Peter; Braun, Werner; Wüthrich, Kurt.

In: Journal of Biomolecular NMR, Vol. 10, No. 4, 1997, p. 351-362.

Research output: Contribution to journalArticle

Mumenthaler, Christian ; Güntert, Peter ; Braun, Werner ; Wüthrich, Kurt. / Automated combined assignment of NOESY spectra and three-dimensional protein structure determination. In: Journal of Biomolecular NMR. 1997 ; Vol. 10, No. 4. pp. 351-362.
@article{c80bb9d324e14fc09ff72c49bd58c4f8,
title = "Automated combined assignment of NOESY spectra and three-dimensional protein structure determination",
abstract = "A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed simultaneously. The input consists of a list of NOESY peak positions and a list of chemical shifts as obtained from sequence-specific resonance assignment. For the present applications of this approach the previously introduced NOAH routine was implemented in the distance geometry program DIANA. As an illustration, experimental 2D and 3D NOESY cross-peak lists of six proteins have been analyzed, for which complete sequence-specific 1H assignments are available for the polypeptide backbone and the amino acid side chains. The automated method assigned 70-90{\%} of all NOESY cross peaks, which is on average 10{\%} less than with the interactive approach, and only between 0.8{\%} and 2.4{\%} of the automatically assigned peaks had a different assignment than in the corresponding manually assigned peak lists. The structures obtained with NOAH/DIANA are in close agreement with those from manually assigned peak lists, and with both approaches the residual constraint violations correspond to high-quality NMR structure determinations. Systematic comparisons of the bundles of conformers that represent corresponding automatically and interactively determined structures document the absence of significant bias in either approach, indicating that an important step has been made towards automation of structure determination from NMR spectra.",
keywords = "Error-tolerant target function, NOESY assignment, Protein structure determination",
author = "Christian Mumenthaler and Peter G{\"u}ntert and Werner Braun and Kurt W{\"u}thrich",
year = "1997",
language = "English (US)",
volume = "10",
pages = "351--362",
journal = "Journal of Biomolecular NMR",
issn = "0925-2738",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Automated combined assignment of NOESY spectra and three-dimensional protein structure determination

AU - Mumenthaler, Christian

AU - Güntert, Peter

AU - Braun, Werner

AU - Wüthrich, Kurt

PY - 1997

Y1 - 1997

N2 - A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed simultaneously. The input consists of a list of NOESY peak positions and a list of chemical shifts as obtained from sequence-specific resonance assignment. For the present applications of this approach the previously introduced NOAH routine was implemented in the distance geometry program DIANA. As an illustration, experimental 2D and 3D NOESY cross-peak lists of six proteins have been analyzed, for which complete sequence-specific 1H assignments are available for the polypeptide backbone and the amino acid side chains. The automated method assigned 70-90% of all NOESY cross peaks, which is on average 10% less than with the interactive approach, and only between 0.8% and 2.4% of the automatically assigned peaks had a different assignment than in the corresponding manually assigned peak lists. The structures obtained with NOAH/DIANA are in close agreement with those from manually assigned peak lists, and with both approaches the residual constraint violations correspond to high-quality NMR structure determinations. Systematic comparisons of the bundles of conformers that represent corresponding automatically and interactively determined structures document the absence of significant bias in either approach, indicating that an important step has been made towards automation of structure determination from NMR spectra.

AB - A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed simultaneously. The input consists of a list of NOESY peak positions and a list of chemical shifts as obtained from sequence-specific resonance assignment. For the present applications of this approach the previously introduced NOAH routine was implemented in the distance geometry program DIANA. As an illustration, experimental 2D and 3D NOESY cross-peak lists of six proteins have been analyzed, for which complete sequence-specific 1H assignments are available for the polypeptide backbone and the amino acid side chains. The automated method assigned 70-90% of all NOESY cross peaks, which is on average 10% less than with the interactive approach, and only between 0.8% and 2.4% of the automatically assigned peaks had a different assignment than in the corresponding manually assigned peak lists. The structures obtained with NOAH/DIANA are in close agreement with those from manually assigned peak lists, and with both approaches the residual constraint violations correspond to high-quality NMR structure determinations. Systematic comparisons of the bundles of conformers that represent corresponding automatically and interactively determined structures document the absence of significant bias in either approach, indicating that an important step has been made towards automation of structure determination from NMR spectra.

KW - Error-tolerant target function

KW - NOESY assignment

KW - Protein structure determination

UR - http://www.scopus.com/inward/record.url?scp=0031304082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031304082&partnerID=8YFLogxK

M3 - Article

VL - 10

SP - 351

EP - 362

JO - Journal of Biomolecular NMR

JF - Journal of Biomolecular NMR

SN - 0925-2738

IS - 4

ER -