TITLE:

COMPUTATIONAL METHODS IN STRUCTURAL GENOMICS: HIGH THROUGHPUT PROTEIN STRUCTURE DETERMINATION FROM NMR SPECTRA (No. 23)

DATE:

Friday, October 17th, 2003

TIME:

3:30 PM

LOCATION:

GMCS 214

SPEAKER:

Homayoun Valafar, Southeast collaboratory on structural Genomics, University of Georgia

ABSTRACT:

One of the long-term objectives of structural genomics and bioinformatics initiatives is the development of tools to deduce protein structure and function exclusively from its primary sequence. An underlying requirement for the realization of this objective is the existence of an unbiased and representative database of protein structures. Currently the protein-data-bank (PDB, www.rcsb.org) consists of approximately 22,000 protein structures. It has been speculated that there may be a limited number of fold families; as few as one to several thousand families of structures. Contrary to intuitive expectation, these 22,000 stuctures only represent approximately 700 fold families. This alarming statistic indicates an inadequete target selection procedures and nearly more than 90% redundancy in protein structure determination efforts. This inefficiency in protein structure determination will result a significant delay in completion of a comprehensive structural database.

On this path, NMR spectroscopy can play an important role in the realization of the global objectives of the structural genomics initiative. NMR spectroscopic techniques can not only provide powerful tools for structure elucidation [1] and for the study of molecular interaction [5], they can also be used as powerful screening tools[3]. These screening tools contribute to the overall objective of structural genomics by providing information such as appropriate folding of a protein, interesting target selection[4] and perhaps even identification of proteins more amenable to NMR studies than crystallization trials.

In this presentation we highlight various computational methods that utilize orientational constraints obtained from residual dipolar couplings (RDC)[2]. These computational methods utilize the RDCs obtained from various nuclear interactions in order to facilitate high throughput protein structure determination, rapid identification of novel protein folds and the assessment of the protein fold condition.

References:

1.Tian, F., H. Valafar and J. H. Prestegard (2001). “A dipolar coupling based strategy for simultaneous resonance assignment and structure determination of protein backbones.” Journal of the American Chemical Society 123(47): 11791-11796.

2.Prestegard, J. H., H. M. Al-Hashimi and J. R. Tolman (2000). “NMR structures of biomolecules using field oriented media and residual dipolar couplings.” Quarterly Reviews of Biophysics 33(4): 371-424.

3.Prestegard JH, Valafar H, Glushka J, et al. Nuclear magnetic resonance in the era of structural genomics BIOCHEMISTRY-US 40 (30): 8677-8685 JUL 31 2001

4.Valafar H., J. H. Prestegard, Rapid classification of a protein fold family using a statistical analysis of dipolar couplings, BIOINFORMATICS Vol. 19 2003.

5.Umemoto K, Leffler H, Venot A, et al., Conformational differences in liganded and unliganded states of Galectin-3, BIOCHEMISTRY-US 42 (13): 3688-3695 APR 8 2003

HOST:

Jose Castillo

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