INSERM, UMR-S 665, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Paris, France.
PLoS One. 2012;7(6):e38805. doi: 10.1371/journal.pone.0038805. Epub 2012 Jun 22.
The constant increase in the number of solved protein structures is of great help in understanding the basic principles behind protein folding and evolution. 3-D structural knowledge is valuable in designing and developing methods for comparison, modelling and prediction of protein structures. These approaches for structure analysis can be directly implicated in studying protein function and for drug design. The backbone of a protein structure favours certain local conformations which include α-helices, β-strands and turns. Libraries of limited number of local conformations (Structural Alphabets) were developed in the past to obtain a useful categorization of backbone conformation. Protein Block (PB) is one such Structural Alphabet that gave a reasonable structure approximation of 0.42 Å. In this study, we use PB description of local structures to analyse conformations that are preferred sites for structural variations and insertions, among group of related folds. This knowledge can be utilized in improving tools for structure comparison that work by analysing local structure similarities. Conformational differences between homologous proteins are known to occur often in the regions comprising turns and loops. Interestingly, these differences are found to have specific preferences depending upon the structural classes of proteins. Such class-specific preferences are mainly seen in the all-β class with changes involving short helical conformations and hairpin turns. A test carried out on a benchmark dataset also indicates that the use of knowledge on the class specific variations can improve the performance of a PB based structure comparison approach. The preference for the indel sites also seem to be confined to a few backbone conformations involving β-turns and helix C-caps. These are mainly associated with short loops joining the regular secondary structures that mediate a reversal in the chain direction. Rare β-turns of type I' and II' are also identified as preferred sites for insertions.
不断增加的已解决蛋白质结构数量有助于理解蛋白质折叠和进化背后的基本原理。三维结构知识对于设计和开发比较、建模和预测蛋白质结构的方法非常有价值。这些结构分析方法可以直接用于研究蛋白质功能和药物设计。蛋白质结构的骨架有利于某些局部构象，包括α-螺旋、β-折叠和转角。过去已经开发了数量有限的局部构象库（结构字母表），以对骨架构象进行有用的分类。蛋白质块（PB）是这样的结构字母表之一，它给出了合理的结构近似值为 0.42 Å。在这项研究中，我们使用 PB 描述局部结构来分析在相关折叠组中优先发生结构变化和插入的构象。这种知识可用于改进通过分析局部结构相似性来工作的结构比较工具。同源蛋白质之间的构象差异经常发生在由转角和环组成的区域。有趣的是，这些差异具有特定的偏好，这取决于蛋白质的结构类别。这种特定于类别的偏好主要在全β类中看到，涉及短螺旋构象和发夹转角的变化。在基准数据集上进行的测试也表明，使用关于类特异性变化的知识可以提高基于 PB 的结构比较方法的性能。插入缺失位点的偏好似乎也仅限于涉及β-转角和螺旋 C-帽的几种骨架构象。这些主要与连接规则二级结构的短环有关，它们介导链方向的反转。还确定了罕见的 I'型和 II'型 I 型转角作为插入的首选位点。
