Nucleic Acids Research Advance Access originally published online on November 27, 2006
Nucleic Acids Research 2006 34(22):6540-6548; doi:10.1093/nar/gkl901
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Nucleic Acids Research, 2006, Vol. 34, No. 22 6540-6548
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Sequence comparison by sequence harmony identifies subtype-specific functional sites
Centre for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit De Boelelaan 1081A, 1081 HV Amsterdam, The Netherlands
*To whom correspondence should be addressed. Tel: +31 20 59 87649; Fax: +31 20 59 87653; Email: heringa{at}few.vu.nl
Received July 10, 2006. Revised October 12, 2006. Accepted October 13, 2006.
Multiple sequence alignments are often used to reveal functionally important residues within a protein family. They can be particularly useful for the identification of key residues that determine functional differences between protein subfamilies. We present a new entropy-based method, Sequence Harmony (SH) that accurately detects subfamily-specific positions from a multiple sequence alignment. The SH algorithm implements a novel formula, able to score compositional differences between subfamilies, without imposing conservation, in a simple manner on an intuitive scale. We compare our method with the most important published methods, i.e. AMAS, TreeDet and SDP-pred, using three well-studied protein families: the receptor-binding domain (MH2) of the Smad family of transcription factors, the Ras-superfamily of small GTPases and the MIP-family of integral membrane transporters. We demonstrate that SH accurately selects known functional sites with higher coverage than the other methods for these test-cases. This shows that compositional differences between protein subfamilies provide sufficient basis for identification of functional sites. In addition, SH selects a number of sites of unknown function that could be interesting candidates for further experimental investigation.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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