Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee

Background: Transmembrane proteins (TMPs) constitute about 20 similar to 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 T) 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 T. 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 http://tcoffee.crg.cat/tmcoffee and a freeware open source code can be downloaded from http://www.tcoffee.org/Packages/Stable/Latest.