STATISTICS OF PROTEIN THREADING

现在普遍承认在序列和结构比较中需要严格的统计，特别是鉴于NCBI的BLAST程序套件的成功。从将统计学应用于序列问题到将其应用于结构问题，显然是整理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固定蛋白质残基之间相互作用的方向和距离的管（二级结构）。查询序列中的残基就像一串不同颜色的珠子。将珠子串穿过管，直到蛋白质残基之间的相互作用尽可能有利。于是问题就出现了：所发现的最有利的交互是仅仅与偶然性一致，还是它指示查询序列结构与试验性线程结构的系统相似性？我们对统计显著性有一些令人鼓舞的初步估计，因为它们系统地、一致地高估了真实的p值，大约是300倍。我们目前正在探索蛋白质结构相关性，产生这种高估，以纠正它。一份关于统计近似的论文已经发表，在未来的一年里，这个项目将由一个到达的博士后进行。- 结构数据库，统计显著性，线索，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