Automated assignment of simulated and experimental NOESY spectra of proteins by feedback filtering and self-correcting distance geometry

Ch Mumenthaler, Werner Braun

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

A new method for automatically assigning proton-proton NOESY spectra is described and demonstrated for simulated and experimental spectra of the proteins dendrotoxin K, α-amylase inhibitor tendamistat and the DNA-binding domain of the 434 repressor protein. The method assigns the NOESY spectrum and calculates three-dimensional protein structures simultaneously, using a list of proton chemical shifts and 3J(NHα) coupling constants. An ensemble of structures is iteratively calculated by self-correcting distance geometry from unambiguous and selected ambiguous NOESY cross peaks. New structure based filters recognize the correct constraints from the ambiguous cross peak list. For the first round of assignment neither a preliminary initial structure nor a sufficient set of unambiguous NOESY cross peaks is needed. The method can also be applied to cross peak lists containing hundreds of noise peaks. For an assumed tolerance of +/- 0.01 ppm in the chemical shifts of the peak positions, only about 10% of the NOESY cross peaks can be unambiguously assigned based on their chemical shifts alone. Our automated method assigned about 80% of all cross peaks with this chemical shift tolerance, and 95 to 99% of the assignments were correct. The average pairwise RMSD for the backbone atoms of the ten best final structures is about 1.5 Å in all three proteins and the previously determined NMR solution structures are always embedded in this structure bundle. We regard our method as a highly practical tool for automatic calculation of three-dimensional protein structures from NMR spectra with minimal human interference.

Original languageEnglish (US)
Pages (from-to)465-480
Number of pages16
JournalJournal of Molecular Biology
Volume254
Issue number3
DOIs
StatePublished - 1995

Fingerprint

Protons
Proteins
Amylases
Noise
DNA
tendamistate
Bacteriophage 434 434-repressor protein
dendrotoxin K
protein K

Keywords

  • Automated assignment
  • Distance geometry in torsion angles
  • NMR
  • Three-dimensional solution structure

ASJC Scopus subject areas

  • Virology
  • Molecular Biology

Cite this

@article{b21a6a04999842b0b835e8207514dbee,
title = "Automated assignment of simulated and experimental NOESY spectra of proteins by feedback filtering and self-correcting distance geometry",
abstract = "A new method for automatically assigning proton-proton NOESY spectra is described and demonstrated for simulated and experimental spectra of the proteins dendrotoxin K, α-amylase inhibitor tendamistat and the DNA-binding domain of the 434 repressor protein. The method assigns the NOESY spectrum and calculates three-dimensional protein structures simultaneously, using a list of proton chemical shifts and 3J(NHα) coupling constants. An ensemble of structures is iteratively calculated by self-correcting distance geometry from unambiguous and selected ambiguous NOESY cross peaks. New structure based filters recognize the correct constraints from the ambiguous cross peak list. For the first round of assignment neither a preliminary initial structure nor a sufficient set of unambiguous NOESY cross peaks is needed. The method can also be applied to cross peak lists containing hundreds of noise peaks. For an assumed tolerance of +/- 0.01 ppm in the chemical shifts of the peak positions, only about 10{\%} of the NOESY cross peaks can be unambiguously assigned based on their chemical shifts alone. Our automated method assigned about 80{\%} of all cross peaks with this chemical shift tolerance, and 95 to 99{\%} of the assignments were correct. The average pairwise RMSD for the backbone atoms of the ten best final structures is about 1.5 {\AA} in all three proteins and the previously determined NMR solution structures are always embedded in this structure bundle. We regard our method as a highly practical tool for automatic calculation of three-dimensional protein structures from NMR spectra with minimal human interference.",
keywords = "Automated assignment, Distance geometry in torsion angles, NMR, Three-dimensional solution structure",
author = "Ch Mumenthaler and Werner Braun",
year = "1995",
doi = "10.1006/jmbi.1995.0631",
language = "English (US)",
volume = "254",
pages = "465--480",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Automated assignment of simulated and experimental NOESY spectra of proteins by feedback filtering and self-correcting distance geometry

AU - Mumenthaler, Ch

AU - Braun, Werner

PY - 1995

Y1 - 1995

N2 - A new method for automatically assigning proton-proton NOESY spectra is described and demonstrated for simulated and experimental spectra of the proteins dendrotoxin K, α-amylase inhibitor tendamistat and the DNA-binding domain of the 434 repressor protein. The method assigns the NOESY spectrum and calculates three-dimensional protein structures simultaneously, using a list of proton chemical shifts and 3J(NHα) coupling constants. An ensemble of structures is iteratively calculated by self-correcting distance geometry from unambiguous and selected ambiguous NOESY cross peaks. New structure based filters recognize the correct constraints from the ambiguous cross peak list. For the first round of assignment neither a preliminary initial structure nor a sufficient set of unambiguous NOESY cross peaks is needed. The method can also be applied to cross peak lists containing hundreds of noise peaks. For an assumed tolerance of +/- 0.01 ppm in the chemical shifts of the peak positions, only about 10% of the NOESY cross peaks can be unambiguously assigned based on their chemical shifts alone. Our automated method assigned about 80% of all cross peaks with this chemical shift tolerance, and 95 to 99% of the assignments were correct. The average pairwise RMSD for the backbone atoms of the ten best final structures is about 1.5 Å in all three proteins and the previously determined NMR solution structures are always embedded in this structure bundle. We regard our method as a highly practical tool for automatic calculation of three-dimensional protein structures from NMR spectra with minimal human interference.

AB - A new method for automatically assigning proton-proton NOESY spectra is described and demonstrated for simulated and experimental spectra of the proteins dendrotoxin K, α-amylase inhibitor tendamistat and the DNA-binding domain of the 434 repressor protein. The method assigns the NOESY spectrum and calculates three-dimensional protein structures simultaneously, using a list of proton chemical shifts and 3J(NHα) coupling constants. An ensemble of structures is iteratively calculated by self-correcting distance geometry from unambiguous and selected ambiguous NOESY cross peaks. New structure based filters recognize the correct constraints from the ambiguous cross peak list. For the first round of assignment neither a preliminary initial structure nor a sufficient set of unambiguous NOESY cross peaks is needed. The method can also be applied to cross peak lists containing hundreds of noise peaks. For an assumed tolerance of +/- 0.01 ppm in the chemical shifts of the peak positions, only about 10% of the NOESY cross peaks can be unambiguously assigned based on their chemical shifts alone. Our automated method assigned about 80% of all cross peaks with this chemical shift tolerance, and 95 to 99% of the assignments were correct. The average pairwise RMSD for the backbone atoms of the ten best final structures is about 1.5 Å in all three proteins and the previously determined NMR solution structures are always embedded in this structure bundle. We regard our method as a highly practical tool for automatic calculation of three-dimensional protein structures from NMR spectra with minimal human interference.

KW - Automated assignment

KW - Distance geometry in torsion angles

KW - NMR

KW - Three-dimensional solution structure

UR - http://www.scopus.com/inward/record.url?scp=0029610793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029610793&partnerID=8YFLogxK

U2 - 10.1006/jmbi.1995.0631

DO - 10.1006/jmbi.1995.0631

M3 - Article

VL - 254

SP - 465

EP - 480

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 3

ER -