Touring protein fold space with Dali/FSSP.

The FSSP database and its new supplement, the Dali Domain Dictionary, present a continuously updated classification of all known 3D protein structures. The classification is derived using an automatic structure alignment program (Dali) for the all-against-all comparison of structures in the Protein Data Bank. From the resulting enumeration of structural neighbours (which form a surprisingly continuous distribution in fold space) we derive a discrete fold classification in three steps: (i) sequence-related families are covered by a representative set of protein chains; (ii) protein chains are decomposed into structural domains based on the recurrence of structural motifs; (iii) folds are defined as tight clusters of domains in fold space. The fold classification, domain definitions and test sets for sequence-structure alignment (threading) are accessible on the web at www.embl-ebi.ac.uk/dali . The web interface provides a rich network of links between neighbours in fold space, between domains and proteins, and between structures and sequences leading, for example, to a database of explicit multiple alignments of protein families in the twilight zone of sequence similarity. The Dali/FSSP organization of protein structures provides a map of the currently known regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination.

FSSP数据库（FSSP Database）及其新增补数据集Dali结构域词典（Dali Domain Dictionary）提供了针对所有已知三维蛋白质结构的持续更新分类体系。该分类依托自动结构比对程序（Dali）完成，通过对蛋白质数据库（Protein Data Bank）内的所有蛋白质结构开展全对全比对分析。基于由此得到的结构邻体（structural neighbours）枚举结果——这些邻体在折叠空间（fold space）中呈现出出人意料的连续分布特征——我们通过三个步骤构建离散折叠分类体系：(i) 以一组代表性蛋白质链覆盖所有序列相关的蛋白质家族；(ii) 基于结构基序（structural motifs）的重复出现特征，将蛋白质链拆解为多个结构域（structural domains）；(iii) 将折叠定义为折叠空间中结构域的紧密簇集。
折叠分类、结构域定义以及用于序列-结构比对（穿线法，threading）的测试集均可通过以下网址访问：www.embl-ebi.ac.uk/dali。该网页界面搭建了覆盖多维度关联的丰富网络：包括折叠空间内结构邻体之间、结构域与对应蛋白质之间，以及蛋白质结构与序列之间的关联，例如可导向至序列相似性模糊区（twilight zone of sequence similarity）内蛋白质家族的显式多重比对数据库。
这套基于Dali/FSSP框架的蛋白质结构分类体系，绘制出了当前已知的蛋白质宇宙（protein universe）区域图谱，可为折叠原理分析、蛋白质家族的进化归并研究，以及最大化实验结构测定的信息收益提供关键支撑。