INSERM, UMR-S 665, Dynamique des Structures et Interactions des Macromolécules Biologiques, 6, rue Alexandre Cabanel, 75739 Paris Cedex 15, France.
Biochimie. 2012 Sep;94(9):2025-34. doi: 10.1016/j.biochi.2012.05.028. Epub 2012 Jun 4.
Comparison of multiple protein structures has a broad range of applications in the analysis of protein structure, function and evolution. Multiple structure alignment tools (MSTAs) are necessary to obtain a simultaneous comparison of a family of related folds. In this study, we have developed a method for multiple structure comparison largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a 1D sequence string. A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment (mulPBA). Highly similar stretches identified by the pairwise alignments are given higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a three dimensional fit of the structures followed by an iterative refinement of the structural superposition. Systematic comparisons using benchmark datasets of MSTAs underlines that the alignment quality is better than MULTIPROT, MUSTANG and the alignments in HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible MSTAs also indicate that mulPBA alignments are superior to most of the rigid-body MSTAs and highly comparable to the flexible alignment methods.
比较多个蛋白质结构在分析蛋白质结构、功能和进化方面具有广泛的应用。需要使用多个结构比对工具（MSTAs）来同时比较一系列相关的折叠。在这项研究中，我们开发了一种主要基于序列比对技术的多结构比较方法。广泛使用的结构字母表名为 Protein Blocks（PBs），用于将关于 3D 蛋白质骨架构象的信息转换为 1D 序列字符串。采用类似于 CLUSTALW 的渐进比对策略进行多 PB 序列比对（mulPBA）。在比对过程中，通过两两比对识别出的高度相似的片段会被赋予更高的权重。来自 PB 比对的残基等价物用于获得结构的三维拟合，然后对结构叠加进行迭代细化。使用 MSTAs 的基准数据集进行系统比较，突出了在 85%以上的情况下，该比对方法的质量优于 MULTIPROT、MUSTANG 和 HOMSTRAD 中的比对。与其他刚体和柔性 MSTAs 的比较也表明，mulPBA 比对优于大多数刚体 MSTAs，并且与柔性比对方法高度可比。
