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Bioinformatics Vol. 16 no. 7 2000
Pages 613-618
© 2000 Oxford University Press


Original Paper

Domain size distributions can predict domain boundaries

S. J. Wheelan 1,2, A. Marchler-Bauer 1 and S. H. Bryant 1,*

1 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA
2 Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Received on July 17, 1999 ; revised on January 9, 2000 ; accepted on February 10, 2000

Motivation: The sizes of protein domains observed in the 3D-structure database follow a surprisingly narrow distribution. Structural domains are furthermore formed from a single-chain continuous segment in over 80% of instances. These observations imply that some choices of domain boundaries on an otherwise uncharacterized sequence are more likely than others, based solely on the size and segment number of predicted domains. This property might be used to guess the locations of protein domain boundaries.

Results: To test this possibility we enumerate putative domain boundaries and calculate their relative likelihood under a probability model that considers only the size and segment number of predicted domains. We ask, in a cross-validated test using sequences with known 3D structure, whether the most likely guesses agree with the observed domain structure. We find that domain boundary predictions are surprisingly successful for sequences up to 400 residues long and that guessing domain boundaries in this way can improve the sensitivity of threading analysis.

Availability: The DGS algorithm, for ‘Domain Guess by Size’, is available as a web service at http://www.ncbi.nlm.nih.gov/dgs. This site also provides the DGS source code.

Contact: bryant{at}ncbi.nlm.nih.gov

* To whom correspondence should be addressed.


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