Comparison of sequence and structure alignments for protein domains

Profile search methods based on protein domain alignments have proven to be useful tools in comparative sequence analysis. Domain alignments used by currently available search methods have been computed by sequence comparison. With the growth of the protein structure database, however, alignments of many domain pairs have also been computed by structure comparison. Here, we examine the extent to which information from these two sources agrees. We measure agreement with respect to identification of homologous regions in each protein, that is, with respect to the location of domain boundaries. We also measure agreement with respect to identification of homologous residue sites by comparing alignments and assessing the accuracy of the molecular models they predict. We find that domain alignments in publicly available collections based on sequence and structure comparison are largely consistent. However, the homologous regions identified by sequence comparison are often shorter than those identified by 3D structure comparison. In addition, when overall sequence similarity is low alignments from sequence comparison produce less accurate molecular models, suggesting that they less accurately identify homologous sites. These observations suggest that structure comparison results might be used to improve the overall accuracy of domain alignment collections and the performance of profile search methods based on them. Proteins 2002;48:439–446. © 2002 Wiley‐Liss, Inc.

[1]  A. Lesk,et al.  The relation between the divergence of sequence and structure in proteins. , 1986, The EMBO journal.

[2]  T L Blundell,et al.  Comparison of solvent-inaccessible cores of homologous proteins: definitions useful for protein modelling. , 1987, Protein engineering.

[3]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[4]  T. P. Flores,et al.  Comparison of conformational characteristics in structurally similar protein pairs , 1993, Protein science : a publication of the Protein Society.

[5]  C. Sander,et al.  The FSSP database of structurally aligned protein fold families. , 1994, Nucleic acids research.

[6]  G J Barton,et al.  Structural features can be unconserved in proteins with similar folds. An analysis of side-chain to side-chain contacts secondary structure and accessibility. , 1994, Journal of molecular biology.

[7]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[8]  S. Henikoff,et al.  Position-based sequence weights. , 1994, Journal of molecular biology.

[9]  C. Sander,et al.  Parser for protein folding units , 1994, Proteins.

[10]  Sean R. Eddy,et al.  Maximum Discrimination Hidden Markov Models of Sequence Consensus , 1995, J. Comput. Biol..

[11]  S. Bryant,et al.  Threading a database of protein cores , 1995, Proteins.

[12]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[13]  R. Doolittle.  The multiplicity of domains in proteins. , 1995, Annual review of biochemistry.

[14]  J F Gibrat,et al.  Surprising similarities in structure comparison. , 1996, Current opinion in structural biology.

[15]  R. Durbin,et al.  Pfam: A comprehensive database of protein domain families based on seed alignments , 1997, Proteins.

[16]  David C. Jones,et al.  CATH--a hierarchic classification of protein domain structures. , 1997, Structure.

[17]  S H Bryant,et al.  A measure of success in fold recognition. , 1997, Trends in biochemical sciences.

[18]  T. Hubbard,et al.  Critical assessment of methods of protein structure prediction (CASP): Round III , 1999, Proteins.

[19]  S H Bryant,et al.  Measures of threading specificity and accuracy , 1997, Proteins.

[20]  M Levitt,et al.  Competitive assessment of protein fold recognition and alignment accuracy , 1997, Proteins.

[21]  Jérôme Gouzy,et al.  The ProDom database of protein domain families , 1998, Nucleic Acids Res..

[22]  Jérôme Gracy,et al.  Automated protein sequence database classification. II. Delineation Of domain boundaries from sequence similarities , 1998, Bioinform..

[23]  J Schultz,et al.  SMART, a simple modular architecture research tool: identification of signaling domains. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Richard Hughey,et al.  Hidden Markov models for detecting remote protein homologies , 1998, Bioinform..

[25]  D T Jones,et al.  A systematic comparison of protein structure classifications: SCOP, CATH and FSSP. , 1999, Structure.

[26]  Olivier Poch,et al.  A comprehensive comparison of multiple sequence alignment programs , 1999, Nucleic Acids Res..

[27]  George D. Rose,et al.  A protein taxonomy based on secondary structure , 1999, Nature Structural Biology.

[28]  Arne Elofsson,et al.  A comparison of sequence and structure protein domain families as a basis for structural genomics , 1999, Bioinform..

[29]  Yanli Wang,et al.  MMDB: Entrez's 3D-structure database , 2003, Nucleic Acids Res..

[30]  S. Bryant,et al.  Identification of homologous core structures , 1999, Proteins.

[31]  W. Pearson,et al.  Evolution of protein sequences and structures. , 1999, Journal of molecular biology.

[32]  A. Murzin.  Structure classification‐based assessment of CASP3 predictions for the fold recognition targets , 1999, Proteins.

[33]  J. M. Sauder,et al.  Large‐scale comparison of protein sequence alignment algorithms with structure alignments , 2000, Proteins.

[34]  M Linial,et al.  Methodologies for target selection in structural genomics. , 2000, Progress in biophysics and molecular biology.

[35]  A. Panchenko,et al.  Combination of threading potentials and sequence profiles improves fold recognition. , 2000, Journal of molecular biology.

[36]  Nathan Linial,et al.  ProtoMap: automatic classification of protein sequences and hierarchy of protein families , 2000, Nucleic Acids Res..

[37]  D. Higgins,et al.  T-Coffee: A novel method for fast and accurate multiple sequence alignment. , 2000, Journal of molecular biology.

[38]  T. Bhat,et al.  The Protein Data Bank and the challenge of structural genomics , 2000, Nature Structural Biology.

[39]  M. Sternberg,et al.  Enhanced genome annotation using structural profiles in the program 3D-PSSM. , 2000, Journal of molecular biology.

[40]  Martin Vingron,et al.  The SYSTERS protein sequence cluster set , 2000, Nucleic Acids Res..

[41]  G J Barton,et al.  Protein structural domains: Analysis of the 3Dee domains database , 2001, Proteins.

[42]  Thomas L. Madden,et al.  Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. , 2001, Nucleic acids research.

[43]  Philip E. Bourne,et al.  A database and tools for 3-D protein structure comparison and alignment using the Combinatorial Extension (CE) algorithm , 2001, Nucleic Acids Res..

[44]  Geoffrey J. Barton,et al.  3Dee: a database of protein structural domains , 2001, Bioinform..

[45]  Alex Bateman,et al.  The InterPro database, an integrated documentation resource for protein families, domains and functional sites , 2001, Nucleic Acids Res..

[46]  Benjamin A. Shoemaker,et al.  CDD: a database of conserved domain alignments with links to domain three-dimensional structure , 2002, Nucleic Acids Res..

[47]  A. Panchenko,et al.  A comparison of position‐specific score matrices based on sequence and structure alignments , 2002, Protein science : a publication of the Protein Society.