Fernandez-Fuentes Narcis, Fiser Andras
Institute of Biological, Environmental and Rural Sciences Aberystwyth University Aberystwyth, Ceredigion, SY23 3DA, UK.
Methods Mol Biol. 2013;932:141-58. doi: 10.1007/978-1-62703-065-6_9.
Proteins can be decomposed into supersecondary structure modules. We used a generic definition of supersecondary structure elements, so-called Smotifs, which are composed of two flanking regular secondary structures connected by a loop, to explore the evolution and current variety of structure building blocks. Here, we discuss recent observations about the saturation of Smotif geometries in protein structures and how it opens new avenues in protein structure modeling and design. As a first application of these observations we describe our loop conformation modeling algorithm, ArchPred that takes advantage of Smotifs classification. In this application, instead of focusing on specific loop properties the method narrows down possible template conformations in other, often not homologous structures, by identifying the most likely supersecondary structure environment that cradles the loop. Beyond identifying the correct starting supersecondary structure geometry, it takes into account information of fit of anchor residues, sterical clashes, match of predicted and observed dihedral angle preferences, and local sequence signal.
蛋白质可以分解为超二级结构模块。我们采用了超二级结构元件的通用定义，即所谓的S基序，它由两个由环连接的侧翼规则二级结构组成，以探索结构构建块的进化和当前的多样性。在这里，我们讨论了关于蛋白质结构中S基序几何形状饱和度的最新观察结果，以及它如何为蛋白质结构建模和设计开辟新途径。作为这些观察结果的第一个应用，我们描述了利用S基序分类的环构象建模算法ArchPred。在这个应用中，该方法不是专注于特定的环特性，而是通过识别最有可能支撑环的超二级结构环境，缩小其他通常非同源结构中可能的模板构象范围。除了识别正确的起始超二级结构几何形状外，它还考虑了锚定残基的匹配信息、空间冲突、预测和观察到的二面角偏好的匹配以及局部序列信号。
