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Protein Sci. Feb 2000; 9(2): 232–241.
PMCID: PMC2144550

Comparison of sequence profiles. Strategies for structural predictions using sequence information.

Abstract

Distant homologies between proteins are often discovered only after three-dimensional structures of both proteins are solved. The sequence divergence for such proteins can be so large that simple comparison of their sequences fails to identify any similarity. New generation of sensitive alignment tools use averaged sequences of entire homologous families (profiles) to detect such homologies. Several algorithms, including the newest generation of BLAST algorithms and BASIC, an algorithm used in our group to assign fold predictions for proteins from several genomes, are compared to each other on the large set of structurally similar proteins with little sequence similarity. Proteins in the benchmark are classified according to the level of their similarity, which allows us to demonstrate that most of the improvement of the new algorithms is achieved for proteins with strong functional similarities, with almost no progress in recognizing distant fold similarities. It is also shown that details of profile calculation strongly influence its sensitivity in recognizing distant homologies. The most important choice is how to include information from diverging members of the family, avoiding generating false predictions, while accounting for entire sequence divergence within a family. PSI-BLAST takes a conservative approach, deriving a profile from core members of the family, providing a solid improvement without almost any false predictions. BASIC strives for better sensitivity by increasing the weight of divergent family members and paying the price in lower reliability. A new FFAS algorithm introduced here uses a new procedure for profile generation that takes into account all the relations within the family and matches BASIC sensitivity with PSI-BLAST like reliability.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. [PMC free article] [PubMed]
  • Aravind L, Koonin EV. Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. J Mol Biol. 1999 Apr 16;287(5):1023–1040. [PubMed]
  • Bairoch A, Bucher P, Hofmann K. The PROSITE database, its status in 1995. Nucleic Acids Res. 1996 Jan 1;24(1):189–196. [PMC free article] [PubMed]
  • Bork P, Gibson TJ. Applying motif and profile searches. Methods Enzymol. 1996;266:162–184. [PubMed]
  • Brenner SE, Chothia C, Hubbard TJ. Assessing sequence comparison methods with reliable structurally identified distant evolutionary relationships. Proc Natl Acad Sci U S A. 1998 May 26;95(11):6073–6078. [PMC free article] [PubMed]
  • Fischer D, Elofsson A, Rice D, Eisenberg D. Assessing the performance of fold recognition methods by means of a comprehensive benchmark. Pac Symp Biocomput. 1996:300–318. [PubMed]
  • Gibrat JF, Madej T, Bryant SH. Surprising similarities in structure comparison. Curr Opin Struct Biol. 1996 Jun;6(3):377–385. [PubMed]
  • Gribskov M, McLachlan AD, Eisenberg D. Profile analysis: detection of distantly related proteins. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4355–4358. [PMC free article] [PubMed]
  • Henikoff S, Henikoff JG. Position-based sequence weights. J Mol Biol. 1994 Nov 4;243(4):574–578. [PubMed]
  • Holm L, Sander C. Dictionary of recurrent domains in protein structures. Proteins. 1998 Oct 1;33(1):88–96. [PubMed]
  • Krogh A, Mian IS, Haussler D. A hidden Markov model that finds genes in E. coli DNA. Nucleic Acids Res. 1994 Nov 11;22(22):4768–4778. [PMC free article] [PubMed]
  • Murzin AG. Structure classification-based assessment of CASP3 predictions for the fold recognition targets. Proteins. 1999;Suppl 3:88–103. [PubMed]
  • Murzin AG, Brenner SE, Hubbard T, Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995 Apr 7;247(4):536–540. [PubMed]
  • Needleman SB, Wunsch CD. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. [PubMed]
  • Orengo CA, Michie AD, Jones S, Jones DT, Swindells MB, Thornton JM. CATH--a hierarchic classification of protein domain structures. Structure. 1997 Aug 15;5(8):1093–1108. [PubMed]
  • Park J, Karplus K, Barrett C, Hughey R, Haussler D, Hubbard T, Chothia C. Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods. J Mol Biol. 1998 Dec 11;284(4):1201–1210. [PubMed]
  • Park J, Teichmann SA, Hubbard T, Chothia C. Intermediate sequences increase the detection of homology between sequences. J Mol Biol. 1997 Oct 17;273(1):349–354. [PubMed]
  • Pawłowski K, Zhang B, Rychlewski L, Godzik A. The Helicobacter pylori genome: from sequence analysis to structural and functional predictions. Proteins. 1999 Jul 1;36(1):20–30. [PubMed]
  • Pearson WR. Empirical statistical estimates for sequence similarity searches. J Mol Biol. 1998 Feb 13;276(1):71–84. [PubMed]
  • Rychlewski L, Zhang B, Godzik A. Fold and function predictions for Mycoplasma genitalium proteins. Fold Des. 1998;3(4):229–238. [PubMed]
  • Rychlewski L, Zhang B, Godzik A. Functional insights from structural predictions: analysis of the Escherichia coli genome. Protein Sci. 1999 Mar;8(3):614–624. [PMC free article] [PubMed]
  • Sander C, Schneider R. The HSSP data base of protein structure-sequence alignments. Nucleic Acids Res. 1993 Jul 1;21(13):3105–3109. [PMC free article] [PubMed]
  • Shindyalov IN, Bourne PE. Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. Protein Eng. 1998 Sep;11(9):739–747. [PubMed]
  • Tatusov RL, Altschul SF, Koonin EV. Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12091–12095. [PMC free article] [PubMed]

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