Mapping the protein universe

Science

Volumn 273, Issue 5275, 1996, Pages 595-602

  Holm, Liisa ^a   Sander, Chris ^a  

^a EUROPEAN BIOINFORMATICS INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALGORITHM; ARTICLE; DATA BASE; EVOLUTION; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN STRUCTURE; SEQUENCE HOMOLOGY; STRUCTURE ANALYSIS; THREE DIMENSIONAL IMAGING;

EID: 0029785147     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.273.5275.595     Document Type: Article

References (62)

1. For more information, see the Swiss-Prot database at http://expasy.hcuge.ch/and the Trembl database at ftp://embl-ebi.ac.uk/pub/databases/trembl/.
2. F. C. Bernstein et al., J. Mol. Biol. 112, 535 (1977); D. R. Stampf, C. E. Felder, J. L. Sussman, Nature 374, 572 (1995); data sets are accessible at www.pdb. bnl.gov. The Protein Data Bank was founded in 1972 as the global repository for macromolecular structure data.
3. F. C. Bernstein et al., J. Mol. Biol. 112, 535 (1977); D. R. Stampf, C. E. Felder, J. L. Sussman, Nature 374, 572 (1995); data sets are accessible at www.pdb. bnl.gov. The Protein Data Bank was founded in 1972 as the global repository for macromolecular structure data.
4. L. Holm and C. Sander, EMBO J. 14, 1287 (1995); P. J. Artymiuk, D. W. Rice, A. R. Poirrette, P. Willett, Nature Struct. Biol. 2, 117 (1995).
5. L. Holm and C. Sander, EMBO J. 14, 1287 (1995); P. J. Artymiuk, D. W. Rice, A. R. Poirrette, P. Willett, Nature Struct. Biol. 2, 117 (1995).
6. L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U.S.A. 37, 729 (1951); ibid., P. 205; D. B. Wetlaufer, Proc. Natl. Acad. Sci. U.S.A. 70, 697 (1973); C. Chothia, Annu. Rev. Biochem. 53, 537 (1984); _ and A. V. Finkelstein, ibid. 59, 100 (1990); B. L. Sibanda and J. M.Thornton, Methods Enzymol. 202, 59 (1991).
7. L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U.S.A. 37, 729 (1951); ibid., P. 205; D. B. Wetlaufer, Proc. Natl. Acad. Sci. U.S.A. 70, 697 (1973); C. Chothia, Annu. Rev. Biochem. 53, 537 (1984); _ and A. V. Finkelstein, ibid. 59, 100 (1990); B. L. Sibanda and J. M.Thornton, Methods Enzymol. 202, 59 (1991).
8. L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U.S.A. 37, 729 (1951); ibid., P. 205; D. B. Wetlaufer, Proc. Natl. Acad. Sci. U.S.A. 70, 697 (1973); C. Chothia, Annu. Rev. Biochem. 53, 537 (1984); _ and A. V. Finkelstein, ibid. 59, 100 (1990); B. L. Sibanda and J. M.Thornton, Methods Enzymol. 202, 59 (1991).
9. L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U.S.A. 37, 729 (1951); ibid., P. 205; D. B. Wetlaufer, Proc. Natl. Acad. Sci. U.S.A. 70, 697 (1973); C. Chothia, Annu. Rev. Biochem. 53, 537 (1984); _ and A. V. Finkelstein, ibid. 59, 100 (1990); B. L. Sibanda and J. M.Thornton, Methods Enzymol. 202, 59 (1991).
10. L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U.S.A. 37, 729 (1951); ibid., P. 205; D. B. Wetlaufer, Proc. Natl. Acad. Sci. U.S.A. 70, 697 (1973); C. Chothia, Annu. Rev. Biochem. 53, 537 (1984); _ and A. V. Finkelstein, ibid. 59, 100 (1990); B. L. Sibanda and J. M.Thornton, Methods Enzymol. 202, 59 (1991).
11. L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U.S.A. 37, 729 (1951); ibid., P. 205; D. B. Wetlaufer, Proc. Natl. Acad. Sci. U.S.A. 70, 697 (1973); C. Chothia, Annu. Rev. Biochem. 53, 537 (1984); _ and A. V. Finkelstein, ibid. 59, 100 (1990); B. L. Sibanda and J. M.Thornton, Methods Enzymol. 202, 59 (1991).
12. J. S. Richardson, Adv. Protein Chem. 34, 167 (1981).
13. B) that maximizes S.
14. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
15. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
16. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
17. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
18. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
19. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
20. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
21. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
22. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
23. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
24. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
25. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
26. W. R. Taylor, and C. A. Orengo, J. Mol. Biol. 208, 1 (1989); A. Sali and T. L. Blundell, ibid. 212, 403 (1990); G. Vriend and C. Sander, Proteins 11, 52 (1991); M. T. Barakat and P. M. Dean, J. Comp. Aided Mol. Design 5, 107 (1991); N. N. Alexandrov, K. Takahashi, N. Go, J. Mol. Biol. 225, 5 (1992); D. Fischer, O. Bachar, R. Nussinov, H. Wolfson, J. Biomol. Struct. Dyn. 9, 769 (1992); C. A. Orengo, N. P. Brown, W. T. Taylor, Proteins 14, 139 (1992); R. B. Russell and G. J. Barton, ibid., p. 309; H. M. Grindley, P. J. Artymiuk, D. W. Rice, P. Willett, J. Mol. Biol. 229, 707 (1993); L. Holm and C. Sander, ibid. 233, 123 (1993); S. Subbiah, D. V. Laurents, M. Levitt, Curr. Biol. 33, 141 (1993); M. S. Johnson, J. P. Overington, Y. Edwards, A. C. W. May, M. A. Rodionov, in 27th Hawaii International Conference on System Sciences: vol. V, Biotechnology Computing, L. Hunter, Ed. (IEEE Computer Society Press, Los Alamitos, CA, 1994), pp. 296-305; K. Diederichs, Proteins 23, 187 (1995).
27. L. Holm and C. Sander, in Proceedings of the Third International Conference on Intelligent Systems for Molecular Biology, C. Rawlings et al., Eds. (AAAI Press, Menlo Park, CA, 1995), pp. 179-187.
28. R. H. Lathrop, Protein Eng. 7, 1059 (1994).
29. _ and T. F. Smith, J. Mol. Biol. 255, 641 (1996).
30. L. Holm and C. Sander, Proteins 19, 256 (1994).
31. J. P. Noel, H. E. Hamm, P. B. Sigler, Nature 366, 654 (1993).
32. E. F. Pai et al., ibid. 341, 209 (1989).
33. The 3D protein coordinates are sent, via e-mail, to dali@embl-heidelberg.de. The Dali server then returns a list of substructures matching all or part of the query structure or asserts that no significant similarity has been found. Precalculated mutual similarities tor all known protein structures in the Protein Data Bank (2) are also available from http://www.embl-heidelberg.de/dali and can be viewed as alignments or as 3D views with the use of a Web browser.
34. A. M. Lesk, Protein Architecture: A Practical Approach (Oxford Univ. Press, Oxford, 1991).
35. These servers provide Internet access to catalogs of protein 3D structures: Protein Data Bank (http://www. pdb.bnl.gov), Dali (http://www.embl-heidelberg.de/ dali), Scop (http://scop.mrc-lmb.cam.ac.uk/scop/), and CATH (http://www.biochem.ucl.ac.uk/bsm/ cath/).
36. C. Sander and R. Schneider, Proteins 9, 56 (1991).
37. The mean and standard deviations of similarity scores were calibrated against pairwise all-on-all comparisons in a database of 220 proteins, as a function of protein size. Shape similarity quantified with the distance matrix comparison scores (6) can then be expressed in terms of normalized Z scores - that is, standard deviations above the mean.
38. Average linkage clustering assumes that one knows all pairwise similarity scores and proceeds iteratively by grouping the two most similar domains in the set into a class and representing the similarity relative to this class by an average over the similarities relative to its members.
39. L. Holm and C. Sander, Nature 361, 309 (1993).
40. 1/2x), which has a complete set of nonnegative eigenvectors.
41. R. Grantham, C. Gautier, M. Gouy, Nucleic Acids Res. 8, 1893 (1980).
42. A. V. Efimov, J. Mol. Biol. 245, 402 (1995).
43. S. Onesti, P. Brick, D. M. Blow, ibid. 217, 153 (1991).
44. A. V. Finkelstein and B. A. Reva, Nature 351, 497 (1991); A. G. Murzin and A. V. Finkelstein, J. Mol. Biol. 204, 749 (1988); A. M. Lesk, in Combinatorial Pattern Matching, Proceedings of CPM95, Z. Galil and E. Ukkonen, Eds. (Springer, Berlin, 1995), pp. 248-260; G. M. Crippen and V. N. Maiorov, J. Mol. Biol. 252, 144 (1995).
45. A. V. Finkelstein and B. A. Reva, Nature 351, 497 (1991); A. G. Murzin and A. V. Finkelstein, J. Mol. Biol. 204, 749 (1988); A. M. Lesk, in Combinatorial Pattern Matching, Proceedings of CPM95, Z. Galil and E. Ukkonen, Eds. (Springer, Berlin, 1995), pp. 248-260; G. M. Crippen and V. N. Maiorov, J. Mol. Biol. 252, 144 (1995).
46. A. V. Finkelstein and B. A. Reva, Nature 351, 497 (1991); A. G. Murzin and A. V. Finkelstein, J. Mol. Biol. 204, 749 (1988); A. M. Lesk, in Combinatorial Pattern Matching, Proceedings of CPM95, Z. Galil and E. Ukkonen, Eds. (Springer, Berlin, 1995), pp. 248-260; G. M. Crippen and V. N. Maiorov, J. Mol. Biol. 252, 144 (1995).
47. A. V. Finkelstein and B. A. Reva, Nature 351, 497 (1991); A. G. Murzin and A. V. Finkelstein, J. Mol. Biol. 204, 749 (1988); A. M. Lesk, in Combinatorial Pattern Matching, Proceedings of CPM95, Z. Galil and E. Ukkonen, Eds. (Springer, Berlin, 1995), pp. 248-260; G. M. Crippen and V. N. Maiorov, J. Mol. Biol. 252, 144 (1995).
48. M. Sawaya, H. Pelletier, A. Kumar, S. H. Wilson, J. Kraut, Science 264, 1930 (1994); J. Davies et al., Cell 76, 1123 (1994).
49. M. Sawaya, H. Pelletier, A. Kumar, S. H. Wilson, J. Kraut, Science 264, 1930 (1994); J. Davies et al., Cell 76, 1123 (1994).
50. L. Holm and C. Sander, Trends Biochem. Sci. 20, 345 (1995).
51. G. Casari, A. de Daruvar, C. Sander, R. Schneider, Trends Genet. 12, 244 (1996).
52. L. Holm, and C. Sander, Nucleic Acids Res. 22, 3600 (1994); C. Orengo, Curr. Opin. Struct. Biol. 4, 429 (1994); A. G. Murzin, S. E. Brenner, T. Hubbard, C. Chothia, J. Mol. Biol. 247, 536 (1995).
53. L. Holm, and C. Sander, Nucleic Acids Res. 22, 3600 (1994); C. Orengo, Curr. Opin. Struct. Biol. 4, 429 (1994); A. G. Murzin, S. E. Brenner, T. Hubbard, C. Chothia, J. Mol. Biol. 247, 536 (1995).
54. L. Holm, and C. Sander, Nucleic Acids Res. 22, 3600 (1994); C. Orengo, Curr. Opin. Struct. Biol. 4, 429 (1994); A. G. Murzin, S. E. Brenner, T. Hubbard, C. Chothia, J. Mol. Biol. 247, 536 (1995).
55. L. Fairall, J. W. R. Schwabe, L. Chapman, J. T. Finch, D. Rhodes, Nature 366, 483 (1993).
56. W. Kabsch and C. Sander, Biopolymers 22, 2577 (1984).
57. J. G. Omichinski et al., Biochemistry 31, 3907 (1992).
58. T. V. Borchert, M. Mathieu, J. Ph. Zeelen, S. A. Courtneidge, FEBS Lett. 341, 79 (1994).
59. R. W. Pickersgill, G. W. Harris, E. Garman, Acta Crystallogr. B48, 59 (1992).
60. P. Kraulis, J. Appl. Crystallogr. 24, 946 (1991).
61. S. K. Katti, B. A. Katz, H. W. Wyckoff, J. Mol. Biol. 205, 557 (1989).
62. The most recent fold classes among newly determined protein structures as detected by the Dali search system are on Internet under http://www. embl-ebi.ac.uk/dali/newfold/ (for a period of 1 year after publication of this issue). We thank R. Schneider, M. Andrade, K. Sjölander, and J. Sussman for comments on the manuscript, and the EC Biotech and Esprit programs for financial support.