Automated assignment and 3D structure calculations using combinations of 2D homonuclear and 3D heteronuclear NOESY spectra

Numan Oezguen, Larisa Adamian, Yuan Xu, Krishna Rajarathnam, Werner Braun

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance geometry to generate 3D structures from unassigned NOESY spectra. In this study we determined the minimum set of experiments needed to generate a high quality structure bundle. Different combinations of 3D 15N-edited, 13C-edited HSQC-NOESY and 2D homonuclear 1H-1H NOESY spectra of the 77 amino acid protein, myeloid progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD calculations. The quality of the assignments of NOESY cross peaks and the accuracy of the automatically generated 3D structures were compared to those obtained with a conventional manual procedure. Combining data from two types of experiments synergistically increased the number of peaks assigned unambiguously in both individual spectra. As a general trend for the accuracy of the structures we observed structural variations in the backbone fold of the final structures of about 2 Å for single spectral data, of 1 Å to 1.5 Å for double spectral data, and of 0.6 Å for triple spectral data sets. The quality of the assignments and 3D structures from the optimal data using all three spectra were similar to those obtained from traditional assignment methods with structural variations within the bundle of 0.6 Å and 1.3 Å for backbone and heavy atoms, respectively. Almost all constraints (97%) of the automatic NOESY cross peak assignments were cross compatible with the structures from the conventional manual assignment procedure, and an even larger proportion (99%) of the manually derived constraints were compatible with the automatically determined 3D structures. The two mean structures determined by both methods differed only by 1.3 Å rmsd for the backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD analysis of spectra from labeled proteins provides a reliable method for high throughput analysis of genomic targets.

Original languageEnglish (US)
Pages (from-to)249-263
Number of pages15
JournalJournal of Biomolecular NMR
Volume22
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Atoms
Proteins
Experiments
Throughput
Feedback
Amino Acids
Geometry
Spectrum Analysis
Datasets

Keywords

  • Automatic NOESY assignment
  • Automatic structure determination
  • Chemokine
  • DIAMOND
  • Global fold
  • MPIF
  • NOAH

ASJC Scopus subject areas

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

Cite this

Automated assignment and 3D structure calculations using combinations of 2D homonuclear and 3D heteronuclear NOESY spectra. / Oezguen, Numan; Adamian, Larisa; Xu, Yuan; Rajarathnam, Krishna; Braun, Werner.

In: Journal of Biomolecular NMR, Vol. 22, No. 3, 2002, p. 249-263.

Research output: Contribution to journalArticle

@article{b7866cfe93b14fadb8a30ed906d82bf4,
title = "Automated assignment and 3D structure calculations using combinations of 2D homonuclear and 3D heteronuclear NOESY spectra",
abstract = "The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance geometry to generate 3D structures from unassigned NOESY spectra. In this study we determined the minimum set of experiments needed to generate a high quality structure bundle. Different combinations of 3D 15N-edited, 13C-edited HSQC-NOESY and 2D homonuclear 1H-1H NOESY spectra of the 77 amino acid protein, myeloid progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD calculations. The quality of the assignments of NOESY cross peaks and the accuracy of the automatically generated 3D structures were compared to those obtained with a conventional manual procedure. Combining data from two types of experiments synergistically increased the number of peaks assigned unambiguously in both individual spectra. As a general trend for the accuracy of the structures we observed structural variations in the backbone fold of the final structures of about 2 {\AA} for single spectral data, of 1 {\AA} to 1.5 {\AA} for double spectral data, and of 0.6 {\AA} for triple spectral data sets. The quality of the assignments and 3D structures from the optimal data using all three spectra were similar to those obtained from traditional assignment methods with structural variations within the bundle of 0.6 {\AA} and 1.3 {\AA} for backbone and heavy atoms, respectively. Almost all constraints (97{\%}) of the automatic NOESY cross peak assignments were cross compatible with the structures from the conventional manual assignment procedure, and an even larger proportion (99{\%}) of the manually derived constraints were compatible with the automatically determined 3D structures. The two mean structures determined by both methods differed only by 1.3 {\AA} rmsd for the backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD analysis of spectra from labeled proteins provides a reliable method for high throughput analysis of genomic targets.",
keywords = "Automatic NOESY assignment, Automatic structure determination, Chemokine, DIAMOND, Global fold, MPIF, NOAH",
author = "Numan Oezguen and Larisa Adamian and Yuan Xu and Krishna Rajarathnam and Werner Braun",
year = "2002",
doi = "10.1023/A:1014925824100",
language = "English (US)",
volume = "22",
pages = "249--263",
journal = "Journal of Biomolecular NMR",
issn = "0925-2738",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - Automated assignment and 3D structure calculations using combinations of 2D homonuclear and 3D heteronuclear NOESY spectra

AU - Oezguen, Numan

AU - Adamian, Larisa

AU - Xu, Yuan

AU - Rajarathnam, Krishna

AU - Braun, Werner

PY - 2002

Y1 - 2002

N2 - The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance geometry to generate 3D structures from unassigned NOESY spectra. In this study we determined the minimum set of experiments needed to generate a high quality structure bundle. Different combinations of 3D 15N-edited, 13C-edited HSQC-NOESY and 2D homonuclear 1H-1H NOESY spectra of the 77 amino acid protein, myeloid progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD calculations. The quality of the assignments of NOESY cross peaks and the accuracy of the automatically generated 3D structures were compared to those obtained with a conventional manual procedure. Combining data from two types of experiments synergistically increased the number of peaks assigned unambiguously in both individual spectra. As a general trend for the accuracy of the structures we observed structural variations in the backbone fold of the final structures of about 2 Å for single spectral data, of 1 Å to 1.5 Å for double spectral data, and of 0.6 Å for triple spectral data sets. The quality of the assignments and 3D structures from the optimal data using all three spectra were similar to those obtained from traditional assignment methods with structural variations within the bundle of 0.6 Å and 1.3 Å for backbone and heavy atoms, respectively. Almost all constraints (97%) of the automatic NOESY cross peak assignments were cross compatible with the structures from the conventional manual assignment procedure, and an even larger proportion (99%) of the manually derived constraints were compatible with the automatically determined 3D structures. The two mean structures determined by both methods differed only by 1.3 Å rmsd for the backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD analysis of spectra from labeled proteins provides a reliable method for high throughput analysis of genomic targets.

AB - The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance geometry to generate 3D structures from unassigned NOESY spectra. In this study we determined the minimum set of experiments needed to generate a high quality structure bundle. Different combinations of 3D 15N-edited, 13C-edited HSQC-NOESY and 2D homonuclear 1H-1H NOESY spectra of the 77 amino acid protein, myeloid progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD calculations. The quality of the assignments of NOESY cross peaks and the accuracy of the automatically generated 3D structures were compared to those obtained with a conventional manual procedure. Combining data from two types of experiments synergistically increased the number of peaks assigned unambiguously in both individual spectra. As a general trend for the accuracy of the structures we observed structural variations in the backbone fold of the final structures of about 2 Å for single spectral data, of 1 Å to 1.5 Å for double spectral data, and of 0.6 Å for triple spectral data sets. The quality of the assignments and 3D structures from the optimal data using all three spectra were similar to those obtained from traditional assignment methods with structural variations within the bundle of 0.6 Å and 1.3 Å for backbone and heavy atoms, respectively. Almost all constraints (97%) of the automatic NOESY cross peak assignments were cross compatible with the structures from the conventional manual assignment procedure, and an even larger proportion (99%) of the manually derived constraints were compatible with the automatically determined 3D structures. The two mean structures determined by both methods differed only by 1.3 Å rmsd for the backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD analysis of spectra from labeled proteins provides a reliable method for high throughput analysis of genomic targets.

KW - Automatic NOESY assignment

KW - Automatic structure determination

KW - Chemokine

KW - DIAMOND

KW - Global fold

KW - MPIF

KW - NOAH

UR - http://www.scopus.com/inward/record.url?scp=0036217249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036217249&partnerID=8YFLogxK

U2 - 10.1023/A:1014925824100

DO - 10.1023/A:1014925824100

M3 - Article

C2 - 11991354

AN - SCOPUS:0036217249

VL - 22

SP - 249

EP - 263

JO - Journal of Biomolecular NMR

JF - Journal of Biomolecular NMR

SN - 0925-2738

IS - 3

ER -