Recently [1] investigated the occurence of protein pairs with similar-sequence and significant dissimilarity. Using sequence-based structure analysis, they "have found numerous protein pairs, of 50-100% sequence identity, that have dissimilar structures, as measured by RMSDs greater than 3A or 6A." And they have compiled a database [2] of sequence-similar, structuraly dissimilar protein pairs.

"The RMSD between two superimposed structures is usually measured only over those residues that are considered as aligned. ...
In contrast, the RMSD obtained from the structural alignment is much smaller since this RMSD is measured only over residues that occupy similar position in space. ...
In almost all cases, geometry-based structure alignments yield a lower RMSD than sequence-based RMSDs." (Kosloff and Kolodny, 2008)

In particular, they have identified 158 pairs with sequence identity 100% and sequence-based-structure-superposition RMSD ≥ 6A, which are partitioned into 60 clusters.

Shown below are alignments of the pairs obtained by ComSubstruct (+manual inspection)  and the pairwise DaliLite server [4, 5].

(0) Golden standard of  60 representative pairs (one pair from each cluster)

(i) Assignments of the D2 code, DSSP state, PB code, and (phi, psi) angles
and (ii) Structural analysis by the FATCAT, FlexProtRAPIDO, and Dyndom servers
and (iii) Corresponding entries in the MolMovDB database:

  1. Computation of the DSSP state and (phi, psi) angles: http://cubic.bioc.columbia.edu/services/DSSPcont/
  2. Computation of the PB code: http://bioinformatics.univ-reunion.fr/PBE/
  3. The FATCAT server: http://fatcat.burnham.org/
  4. The FlexProt server: http://bioinfo3d.cs.tau.ac.il/FlexProt/
  5. The RAPIDO server: http://webapps.embl-hamburg.de/rapido/
  6. The DynDom server: http://www.sys.uea.ac.uk/dyndom/
  7. The MolMovDB database: http://molmovdb.org/

(1) Local structure analysis of structure-dissimilar pairs (158 pairs with sequence identity 100% and RMSD ≥ 6A)

*"Chameleon sequences" are amino-acid fragments which could adopt different regular secondary structures (i.e., alpha-helix and beta-strand) in proteins. (Corrected on 2008-08-12)

(2) Alignment of structure-dissimilar pairs (158 pairs with sequence identity 100% and RMSD ≥ 6A)  

  1. Kosloff, M. and Kolodny, R. (2008) Sequence-similar, structure-dissimilar protein pairs in the PDB. Proteins: Structure, Function, and Bioinformatics, 71(2): 891-902.
  2. Database of Sequence-Similar, Structure-Dissimilar Protein Pairs in the PDB: http://mt.cs.haifa.ac.il/seqsimstrdiff/seqsimstrdiff_local.htm
  3. Tuinstra, R.L., Peterson, F.C., Kutlesa, S., Elgin, E.S., Kron, M.A., and Volkman, B.F. (2008) Interconversion between two unrelated protein folds in the lymphotactin native state. Proc. Natl. Acad. Sci. USA, 105:5057-5062.
  4. Holm, L. and Park J. (2000) DaliLite workbench for protein structure comparison. Bioinformatics, 16:566-567.
  5. The pairwise DaliLite server : http://www.ebi.ac.uk/DaliLite/