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PEDS Advance Access published online on January 10, 2006

Protein Engineering Design and Selection, doi:10.1093/protein/gzj002
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© The Author (2006). Published by Oxford University Press. All rights reserved.
Received July 12, 2005
Revised November 12, 2005
Accepted November 12, 2005

Article

An empirical approach for detecting nucleotide-binding sites on proteins

Mihoko Saito 1, Mitiko Go 2, and Tsuyoshi Shirai 3 *

1 Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
2 Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8601, Japan; Department of Bioscience, Nagahama Institute of Bioscience and Technology, 1266 Tamura, Nagahama 526-0829, Japan
3 Department of Bioscience, Nagahama Institute of Bioscience and Technology, 1266 Tamura, Nagahama 526-0829, Japan; Department of Computational Biology, Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan; Japan Science and Technology Corporation-Bioinformatics Research and Development

* To whom correspondence should be addressed.
Tsuyoshi Shirai, E-mail: t_shirai{at}nagahama-i-bio.ac.jp


   Abstract

Protein structure data in the PDB (Protein Data Bank) were used to construct empirical scores of nucleotide-protein interactions. A simple strategy to evaluate the spatial distribution of protein atoms around the base moieties of nucleotides was applied to categorize adenine, guanine, nicotinamide and flavin nucleotide-binding sites. In addition to the known nucleotide-binding motifs, the empirical scores detected several other features that were shared among proteins with different folds. The empirical scores were also used to predict the binding sites on protein molecules and a comprehensive test of the prediction system was performed. As a result, adenine, guanine, nicotinamide and flavin sites were detected with efficiencies of 31, 29, 32 and 40%, respectively. The predictions were judged to be successful if the predicted base with the best score was located within a 3.0 Å r.m.s.d. from the known ligand positions.


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