Ilyin Valentin A, Abyzov Alexej, Leslin Chesley M
Biology Department, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Protein Sci. 2004 Jul;13(7):1865-74. doi: 10.1110/ps.04672604.
Similarity of protein structures has been analyzed using three-dimensional Delaunay triangulation patterns derived from the backbone representation. It has been found that structurally related proteins have a common spatial invariant part, a set of tetrahedrons, mathematically described as a common spatial subgraph volume of the three-dimensional contact graph derived from Delaunay tessellation (DT). Based on this property of protein structures, we present a novel common volume superimposition (TOPOFIT) method to produce structural alignments. Structural alignments usually evaluated by a number of equivalent (aligned) positions (N(e)) with corresponding root mean square deviation (RMSD). The superimposition of the DT patterns allows one to uniquely identify a maximal common number of equivalent residues in the structural alignment. In other words, TOPOFIT identifies a feature point on the RMSD N(e) curve, a topomax point, until which the topologies of two structures correspond to each other, including backbone and interresidue contacts, whereas the growing number of mismatches between the DT patterns occurs at larger RMSD (N(e)) after the topomax point. It has been found that the topomax point is present in all alignments from different protein structural classes; therefore, the TOPOFIT method identifies common, invariant structural parts between proteins. The alignments produced by the TOPOFIT method have a good correlation with alignments produced by other current methods. This novel method opens new opportunities for the comparative analysis of protein structures and for more detailed studies on understanding the molecular principles of tertiary structure organization and functionality. The TOPOFIT method also helps to detect conformational changes, topological differences in variable parts, which are particularly important for studies of variations in active/ binding sites and protein classification.
利用从主链表示中导出的三维德劳内三角剖分模式分析了蛋白质结构的相似性。已发现结构相关的蛋白质具有一个共同的空间不变部分，即一组四面体，在数学上被描述为从德劳内镶嵌（DT）导出的三维接触图的一个共同空间子图体积。基于蛋白质结构的这一特性，我们提出了一种新颖的共同体积叠加（TOPOFIT）方法来生成结构比对。结构比对通常通过一些具有相应均方根偏差（RMSD）的等效（对齐）位置（N(e)）来评估。DT模式的叠加允许在结构比对中唯一地识别出最大数量的等效残基。换句话说，TOPOFIT在RMSD N(e)曲线上识别出一个特征点，即拓扑最大值点，直到该点两个结构的拓扑结构相互对应，包括主链和残基间接触，而在拓扑最大值点之后，DT模式之间不匹配的数量在更大的RMSD（N(e)）处出现。已发现拓扑最大值点存在于来自不同蛋白质结构类别的所有比对中；因此，TOPOFIT方法识别出蛋白质之间共同的、不变的结构部分。TOPOFIT方法产生的比对与其他当前方法产生的比对具有良好的相关性。这种新颖的方法为蛋白质结构的比较分析以及更详细地研究三级结构组织和功能的分子原理开辟了新的机会。TOPOFIT方法还有助于检测构象变化、可变部分中的拓扑差异，这对于研究活性/结合位点的变化和蛋白质分类尤为重要。
