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Bioinformatics Vol. 16 no. 9 2000
Pages 760-766
© 2000 Oxford University Press

Original Paper

PHAT: a transmembrane-specific substitution matrix

Pauline C. Ng 1, Jorja G. Henikoff 2 and Steven Henikoff 2,

1 Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
2 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109-1024, USA

Received on February 23, 2000 ; revised on April 14, 2000 ; accepted on April 18, 2000

Motivation: Database searching algorithms for proteins use scoring matrices based on average protein properties, and thus are dominated by globular proteins. However, since transmembrane regions of a protein are in a distinctly different environment than globular proteins, one would expect generalized substitution matrices to be inappropriate for transmembrane regions.

Results: We present the PHAT (predicted hydrophobic and transmembrane) matrix, which significantly outperforms generalized matrices and a previously published transmembrane matrix in searches with transmembrane queries. We conclude that a better matrix can be constructed by using background frequencies characteristic of the twilight zone, where low-scoring true positives have scores indistinguishable from high-scoring false positives, rather than the amino acid frequencies of the database. The PHAT matrix may help improve the accuracy of sequence alignments and evolutionary trees of membrane proteins.

Availability: http://www.blocks.fhcrc.org/~pauline

Contact: steveh{at}muller.fhcrc.org

To whom correspondence should be addressed.


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