Skip to main content

A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS.

Publication ,  Journal Article
Zeng, JM; Tripathy, C; Zhou, P; Donald, BR
Published in: Comput Syst Bioinformatics Conf
2008

High-throughput structure determination based on solution Nuclear Magnetic Resonance (NMR) spectroscopy plays an important role in structural genomics. One of the main bottlenecks in NMR structure determination is the interpretation of NMR data to obtain a sufficient number of accurate distance restraints by assigning nuclear Overhauser effect (NOE) spectral peaks to pairs of protons. The difficulty in automated NOE assignment mainly lies in the ambiguities arising both from the resonance degeneracy of chemical shifts and from the uncertainty due to experimental errors in NOE peak positions. In this paper we present a novel NOE assignment algorithm, called HAusdorff-based NOE Assignment (HANA), that starts with a high-resolution protein backbone computed using only two residual dipolar couplings (RDCs) per residue37, 39, employs a Hausdorff-based pattern matching technique to deduce similarity between experimental and back-computed NOE spectra for each rotamer from a statistically diverse library, and drives the selection of optimal position-specific rotamers for filtering ambiguous NOE assignments. Our algorithm runs in time O(tn(3) +tn log t), where t is the maximum number of rotamers per residue and n is the size of the protein. Application of our algorithm on biological NMR data for three proteins, namely, human ubiquitin, the zinc finger domain of the human DNA Y-polymerase Eta (pol η) and the human Set2-Rpb1 interacting domain (hSRI) demonstrates that our algorithm overcomes spectral noise to achieve more than 90% assignment accuracy. Additionally, the final structures calculated using our automated NOE assignments have backbone RMSD < 1.7 Å and all-heavy-atom RMSD < 2.5 Å from reference structures that were determined either by X-ray crystallography or traditional NMR approaches. These results show that our NOE assignment algorithm can be successfully applied to protein NMR spectra to obtain high-quality structures.

Duke Scholars

Published In

Comput Syst Bioinformatics Conf

ISSN

1752-7791

Publication Date

2008

Volume

2008

Start / End Page

169 / 181

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zeng, J. M., Tripathy, C., Zhou, P., & Donald, B. R. (2008). A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS. Comput Syst Bioinformatics Conf, 2008, 169–181.
Zeng, Jianyang Michael, Chittaranjan Tripathy, Pei Zhou, and Bruce R. Donald. “A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS.Comput Syst Bioinformatics Conf 2008 (2008): 169–81.
Zeng JM, Tripathy C, Zhou P, Donald BR. A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS. Comput Syst Bioinformatics Conf. 2008;2008:169–81.
Zeng, Jianyang Michael, et al. “A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS.Comput Syst Bioinformatics Conf, vol. 2008, 2008, pp. 169–81.
Zeng JM, Tripathy C, Zhou P, Donald BR. A HAUSDORFF-BASED NOE ASSIGNMENT ALGORITHM USING PROTEIN BACKBONE DETERMINED FROM RESIDUAL DIPOLAR COUPLINGS AND ROTAMER PATTERNS. Comput Syst Bioinformatics Conf. 2008;2008:169–181.

Published In

Comput Syst Bioinformatics Conf

ISSN

1752-7791

Publication Date

2008

Volume

2008

Start / End Page

169 / 181

Location

United States