Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee

Area of Science:

• Bioinformatics
• Computational Biology
• Structural Biology

Background:

• Transmembrane proteins (TMPs) represent a significant portion of protein-coding genes but are challenging to align due to a lack of experimental structures.
• Current alignment methods, like PRALINE™, achieve only 50% accuracy on reference datasets.

Purpose of the Study:

• To develop an improved method for multiple sequence alignment of alpha-helical transmembrane proteins.
• To enhance the accuracy and efficiency of transmembrane protein alignment.

Main Methods:

• Adapted homology extension combined with a consistency-based approach.
• Developed TM-Coffee, a specialized mode of PSI-Coffee, utilizing a reduced reference database for homology extension.

Main Results:

• TM-Coffee demonstrates significant improvements in alignment accuracy over leading methods on the BAliBASE2-ref7 dataset for alpha-helical TMPs.
• Utilizing non-redundant UniRef databases for homology extension yields comparable results with reduced computational cost.
• TM-Coffee is integrated into the T-Coffee package, with web server and open-source code available.

Conclusions:

• TM-Coffee offers a substantial advancement in transmembrane protein multiple sequence alignment.
• The method provides a more accurate and computationally efficient approach for analyzing TMPs.
• Availability of TM-Coffee facilitates further research in transmembrane protein structure and function.