Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee

BMC Bioinformatics. 2012 Mar 28;13 Suppl 4(Suppl 4):S1. doi: 10.1186/1471-2105-13-S4-S1.


Background: Transmembrane proteins (TMPs) constitute about 20~30% of all protein coding genes. The relative lack of experimental structure has so far made it hard to develop specific alignment methods and the current state of the art (PRALINE™) only manages to recapitulate 50% of the positions in the reference alignments available from the BAliBASE2-ref7.

Methods: We show how homology extension can be adapted and combined with a consistency based approach in order to significantly improve the multiple sequence alignment of alpha-helical TMPs. TM-Coffee is a special mode of PSI-Coffee able to efficiently align TMPs, while using a reduced reference database for homology extension.

Results: Our benchmarking on BAliBASE2-ref7 alpha-helical TMPs shows a significant improvement over the most accurate methods such as MSAProbs, Kalign, PROMALS, MAFFT, ProbCons and PRALINE™. We also estimated the influence of the database used for homology extension and show that highly non-redundant UniRef databases can be used to obtain similar results at a significantly reduced computational cost over full protein databases. TM-Coffee is part of the T-Coffee package, a web server is also available from and a freeware open source code can be downloaded from

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Databases, Protein
  • Drosophila / chemistry*
  • Drosophila / metabolism
  • Drosophila melanogaster / chemistry*
  • Drosophila melanogaster / metabolism
  • Membrane Proteins / chemistry*
  • Sequence Alignment*
  • Software*


  • Membrane Proteins