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Nucleic Acids Research 2006 34(9):2598-2606; doi:10.1093/nar/gkl274
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Published online 17 May 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

Refining multiple sequence alignments with conserved core regions

Saikat Chakrabarti, Christopher J. Lanczycki, Anna R. Panchenko, Teresa M. Przytycka, Paul A. Thiessen and Stephen H. Bryant*

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD, 20894, USA

*To whom correspondence should be addressed. Tel: 001 301 435 7792; Fax: 001 301 480 9241; E-mail: bryant{at}ncbi.nlm.nih.gov

Received January 11, 2006. Revised February 19, 2006. Accepted April 3, 2006.

Accurate multiple sequence alignments of proteins are very important to several areas of computational biology and provide an understanding of phylogenetic history of domain families, their identification and classification. This article presents a new algorithm, REFINER, that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core (block) model of a protein family. Realignment of each sequence can correct misalignments between a given sequence and the rest of the profile and at the same time preserves the family's overall block model. Large-scale benchmarking studies showed a noticeable improvement of alignment after refinement. This can be inferred from the increased alignment score and enhanced sensitivity for database searching using the sequence profiles derived from refined alignments compared with the original alignments. A standalone version of the program is available by ftp distribution (ftp://ftp.ncbi.nih.gov/pub/REFINER) and will be incorporated into the next release of the Cn3D structure/alignment viewer.


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