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

Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee

Jia-Ming Chang  1 , Paolo Di Tommaso, Jean-François Taly, Cedric Notredame
Affiliations

Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee

Jia-Ming Chang et al. BMC Bioinformatics. .

Abstract

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 http://tcoffee.crg.cat/tmcoffee and a freeware open source code can be downloaded from http://www.tcoffee.org/Packages/Stable/Latest.

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Figures

Figure 1
Figure 1
Typical colour output (tm_html). In this example, the protein Or9a of Drosophila melanogaster and its orthologues of other Drosophila species were aligned with PSITM template. The colour code corresponds to prediction by HMMTOP, where yellow: in loop, red: TM helix, blue: out loop. Notably, the predicted topology of the Or9a set is consistent with the Benton et al.'s conclusion [20].
Figure 2
Figure 2
Line chart of the average TC respect to different e-value thresholds on UniRef50-TM database. The number of homologues is counted by summing all homologues found in eight families and plotted in log10 scale. The standard error of TC score cross eight families is the range of dash line. SP is skipped due to minor change respect to different e-value thresholds.
See this image and copyright information in PMC

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