Refining pairwise sequence alignments of membrane proteins by the incorporation of anchors.
Refining pairwise sequence alignments of membrane proteins by the incorporation of anchors.
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DOI：
10.1371/journal.pone.0239881
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Forrest LR
中科院分区：
文献类型：
--
作者：
Staritzbichler R;Sarti E;Yaklich E;Aleksandrova A;Stamm M;Khafizov K;Forrest LR
初级序列的比对是蛋白质结构、功能和进化分析的基本步骤，也是产生基于同源性的模型的基本步骤。完整的膜蛋白对这种序列比对方法构成了巨大的挑战，因为它们的进化关系可能非常遥远，而且因为高含量的疏水氨基酸降低了它们的复杂性。通常，生物化学或生物物理数据可以告知最佳比对，例如，指示具有共同功能或结构作用的特定位置。目前，如果这些位置不能通过标准的成对序列比对程序正确匹配，则通常通过手动调整以特别的方式处理将这种信息合并到比对中。然而，这样的修改是有问题的，因为它们降低了新匹配位置两侧的对准区域的稳健性和重现性。以前的研究已经引入了限制，作为一种在序列比对期间强加位置匹配的手段，最初是在基因组组装的背景下。在这里，我们引入位置限制，或“锚”作为我们的比对工具AlignMe的一项功能，为阿尔法螺旋膜蛋白的成对全球序列比对提供帮助。将这种方法应用到涉及远相关和低复杂性序列的现实场景中，我们说明了如何使用添加锚点来修改比对，同时仍然保持其余比对的重复性和严密性。可以使用www.Bioinfo.mpg.de/AlignMe/上提供的AlignMe在线版本生成锚定路线。
The alignment of primary sequences is a fundamental step in the analysis of protein structure, function, and evolution, and in the generation of homology-based models. Integral membrane proteins pose a significant challenge for such sequence alignment approaches, because their evolutionary relationships can be very remote, and because a high content of hydrophobic amino acids reduces their complexity. Frequently, biochemical or biophysical data is available that informs the optimum alignment, for example, indicating specific positions that share common functional or structural roles. Currently, if those positions are not correctly matched by a standard pairwise sequence alignment procedure, the incorporation of such information into the alignment is typically addressed in an ad hoc manner, with manual adjustments. However, such modifications are problematic because they reduce the robustness and reproducibility of the aligned regions either side of the newly matched positions. Previous studies have introduced restraints as a means to impose the matching of positions during sequence alignments, originally in the context of genome assembly. Here we introduce position restraints, or “anchors” as a feature in our alignment tool AlignMe, providing an aid to pairwise global sequence alignment of alpha-helical membrane proteins. Applying this approach to realistic scenarios involving distantly-related and low complexity sequences, we illustrate how the addition of anchors can be used to modify alignments, while still maintaining the reproducibility and rigor of the rest of the alignment. Anchored alignments can be generated using the online version of AlignMe available at www.bioinfo.mpg.de/AlignMe/.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
3
作者：
Chakrabarti S;Bhardwaj N;Anand PA;Sowdhamini R
通讯作者：
Sowdhamini R
影响因子：
5.6
作者：
Myers-Turnbull D;Bliven SE;Rose PW;Aziz ZK;Youkharibache P;Bourne PE;Prlić A
通讯作者：
Prlić A
影响因子：
3
作者：
Chang JM;Di Tommaso P;Taly JF;Notredame C
通讯作者：
Notredame C
影响因子：
3
作者：
di Luccio E;Koehl P
通讯作者：
Koehl P