"The existence of evolutionarily related proteins that possess different folds brings new challenges to the homology modeling techniques and the structure classification stratagies and offers new opportunities for protein design in experimental studies." (Grishin, 2001)

Four mechanisms of fold change in evolution (examples given in [1])  

  1.   Addition/Deletion/Substitution

  2.   Circular Permutation

  3.   Strand Invasion/Withdrawal

  4.   Beta-hairpin Flip/Swap
  * Examples are provided with ComSubstruct and the pairwise DaliLite server [5, 6].

  1. Grishin, N.V. (2001) Fold change in evolution of protein structures. J. Struct. Biol., 134:167-185.
  2. Krishna, S.S. and Grishin, N.V. (2004) Structural drift: a possible pathe to protein fold change. Bioinformatics, 21(8):1308-1310.
  3. Andreeva, A. and Murzin, A.G. (2006) Evolution of protein fold in the presence of functional constraits.
    Curr. Opin. Struct. Biol., 16: 399-408.
  4. Xie, L. and Bourne, E. (2008) Detecting evolutionary relationships across existing fold space, using sequence order-independent profile-profile alignments. Proc. Natl. Acad. Sci. USA, 105:5441-5446.
  5. Holm, L. and Park J. (2000) DaliLite workbench for protein structure comparison. Bioinformatics, 16:566-567.
  6. The pairwise DaliLite server : http://www.ebi.ac.uk/DaliLite/

[Correction] Grishin, D.G. ==> Grishin, N.V.  (2008-09-26)