Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee.

Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee.
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DOI:
10.1186/1471-2105-13-s4-s1
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发表时间:
2012-03-28
期刊:
影响因子:
3
通讯作者:
Notredame C
Notredame C
中科院分区:
生物学4区
文献类型:
--
作者:
Chang JM;Di Tommaso P;Taly JF;Notredame C

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跨膜蛋白(Transmembrane proteins,TMPs)约占所有蛋白质编码基因的20~30%。迄今为止,相对缺乏实验结构使得难以开发特定的比对方法,并且现有技术(PRALINE™)仅设法概括可从BAliBASE 2-ref 7获得的参考比对中的50%的位置。我们展示了如何同源性延伸可以适应,并结合基于一致性的方法,以显着提高多序列比对的α-螺旋TMP。TM-Coffee是PSI-Coffee的一种特殊模式,能够有效地比对TMP,同时使用简化的参考数据库进行同源性延伸。我们对BAliBASE 2-ref 7 α-螺旋TMP的基准测试显示,与MSAProbs、Kalign、PROMALS、MAFFT、ProbCons和PRALINE™等最准确的方法相比,有了显著的改进。我们还估计了用于同源性延伸的数据库的影响,并表明高度非冗余的UniRef数据库可以用于获得类似的结果,在一个显着降低的计算成本超过全蛋白质数据库。TM咖啡是T咖啡包的一部分,一个网络服务器也可以从http://tcoffee.crg.cat/tmcoffee获得,一个免费的开源代码可以从http://www.tcoffee.org/Packages/Stable/Latest下载。
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. 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. 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.