STATISTICS OF PROTEIN THREADING

在序列和结构比较中需要严格的统计数据现在已经被普遍承认，特别是考虑到NCBI BLAST套件项目的成功。从在序列问题中应用统计转向在结构问题中应用统计，显然是理清蛋白质之间遥远关系的下一步。蛋白质线程是获取查询序列并测试其匹配结构数据库成员的能力的操作。这些结构可以被认为是为蛋白质残基之间的相互作用固定方向和距离的管（二级结构）。查询序列中的残数就像字符串中不同颜色的珠子。一串珠子穿过管子，直到蛋白质残基之间的相互作用尽可能有利。那么问题来了：所发现的最有利的交互是偶然发现的，还是表明查询序列结构与试探性线程结构具有系统的相似性？我们对统计显著性的一些初步估计是令人鼓舞的，因为它们系统地、持续地将真实p值高估了大约300倍。我们目前正在探索产生这种高估的蛋白质结构相关性，以纠正它。一篇关于统计近似的论文已经发表，在接下来的一年里，这个项目将由一名到达的博士后继续进行。-结构数据库，统计显著性，线程，序列结构关系

The need for rigorous statistics in sequence and structure comparison is now generally conceded, particularly in light of the success of the BLAST suite of programs at NCBI. Moving from applying statistics in sequence problems to applying them in structure problems is clearly the next step in sorting out distant relations between proteins. Protein threading is the operation of taking a query sequence, and testing its ability to match members of a structural database. The structures may be thought of as tubes (secondary structures) that fix orientations and distances for interactions between protein residues. The residues in the query sequence are like differently colored beads in a string. The string of beads is threaded through the tubes until interactions between the protein residues are as favorable as possible. The question then arises: is the most favorable interaction discovered consistent with chance alone, or does it indicate a systematic similarity of query sequences structure with the tentative threading structure? We have some initial approximations to the statistical significance that are encouraging, in that they systematically and consistently overestimate the true p-values by a factor of about 300. We are currently exploring the protein structural correlations that produce this overestimate, to correct it. A paper has been published on the statistical approximation, and in the coming year, this project will be carried forward by an arriving post-doc. - structural database, statistical significance, threading, sequence-structure relationships