HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Panchenko, A. R. Articles by Bryant, S. H. Search for Related Content PubMed PubMed Citation Articles by Panchenko, A. R. Articles by Bryant, S. H. Social Bookmarking                   What's this?

A comparison of position-specific score matrices based on sequence and structure alignments

Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA

Stephen H. Bryant, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, Room 8N805, 8600 Rockville Pike, Bethesda, MD 20894; e-mail:bryant{at}ncbi.nlm.nih.gov; fax: (301) 435-7794.

Sequence comparison methods based on position-specific score matrices (PSSMs) have proven a useful tool for recognition of the divergent members of a protein family and for annotation of functional sites. Here we investigate one of the factors that affects overall performance of PSSMs in a PSI-BLAST search, the algorithm used to construct the seed alignment upon which the PSSM is based. We compare PSSMs based on alignments constructed by global sequence similarity (ClustalW and ClustalW-pairwise), local sequence similarity (BLAST), and local structure similarity (VAST). To assess performance with respect to identification of conserved functional or structural sites, we examine the accuracy of the three-dimensional molecular models predicted by PSSM-sequence alignments. Using the known structures of those sequences as the standard of truth, we find that model accuracy varies with the algorithm used for seed alignment construction in the pattern local-structure (VAST) > local-sequence (BLAST) > global-sequence (ClustalW). Using structural similarity of query and database proteins as the standard of truth, we find that PSSM recognition sensitivity depends primarily on the diversity of the sequences included in the alignment, with an optimum around 30–50% average pairwise identity. We discuss these observations, and suggest a strategy for constructing seed alignments that optimize PSSM-sequence alignment accuracy and recognition sensitivity.

Keywords: Profile search; protein structure alignment; alignment accuracy

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. K. Shah, P. Aloy, P. Bork, and R. B. Russell Structural similarity to bridge sequence space: Finding new families on the bridges Protein Sci., May 1, 2005; 14(5): 1305 - 1314. [Abstract] [Full Text] [PDF]

				H. D. Cho, C. L. Verlinde, and A. M. Weiner Archaeal CCA-adding Enzymes: CENTRAL ROLE OF A HIGHLY CONSERVED {beta}-TURN MOTIF IN RNA POLYMERIZATION WITHOUT TRANSLOCATION J. Biol. Chem., March 11, 2005; 280(10): 9555 - 9566. [Abstract] [Full Text] [PDF]

				A. R. Panchenko, F. Kondrashov, and S. Bryant Prediction of functional sites by analysis of sequence and structure conservation Protein Sci., April 1, 2004; 13(4): 884 - 892. [Abstract] [Full Text] [PDF]

				A. R. Panchenko Finding weak similarities between proteins by sequence profile comparison Nucleic Acids Res., January 15, 2003; 31(2): 683 - 689. [Abstract] [Full Text] [PDF]