PROTEIN THREADING METHODS

我们已经开发了计算机方法来比较蛋白质序列与结构数据库中的折叠库。该序列贯穿于不同的结构中，最相容的结构通过使用接触势的能量计算来确定。由于它们直接检测结构相似性，线程方法可以识别通过序列比较无法检测到的非常遥远的进化关系。今年的研究重点是测试核心元素线程方法、盲预测和控制实验，以及改进算法以提高灵敏度。使用已知结构的控制实验确定了成功折叠识别和准确建模的阈值：相似的核心亚结构必须包含60%或更多的蛋白质，并且必须重叠到2.5埃或更小的残差，这样才能保留大部分接触。1996年CASP2研讨会（结构预测关键评估）的预测分析证实了这一结论。然而，在某些远距离关系的情况下，结构相似性可以不那么广泛，并且已经考虑了几种提高灵敏度的改进方法。根据与已知结构在同源物中重叠的区域来定义数据库结构的核心，已经被证明可以减少线程预测中的假阴性。接触电位与序列基序评分的结合也显示出在困难的识别问题中增加敏感性。使用严格的p值计算被证明可以减少误报。有了这些改进，折叠识别有望可靠地检测出更大比例的远距离进化关系。这在1998年的CASP3研讨会上得到了证明，NCBI团队在90多个参加比赛的国际团队中获得了折叠认可的第一名。-蛋白质穿线折叠识别结构预测-既不是人体受试者也不是人体组织

We have developed computer methods to compare a proteins sequence with a library of folds from the structural database. The sequence is threaded through alternative structures, and those most compatible are identified by energy calculations, using contact potentials. Since they directly detect structural similarity, threading methods can identify very distant evolutionary relationships that may be undetectable by sequence comparison. Research this year has focused on testing of the core-element threading method, in blind predictions and control experiments, and on algorithmic improvements to increase sensitivity. Control experiments using known structures identified thresholds for successful fold recognition and accurate modeling: the similar core substructure must comprise 60% or more of the protein and must superpose to a residual of 2.5 Angstroms or less, such that a large fraction of contacts are preserved. Analysis of predictions for the 1996 CASP2 workshop (Critical Assessment of Structure Prediction) confirmed this conclusion. Structural similarity can be less extensive in some cases of distant relationship, however, and several improvements to increase sensitivity have been considered. New definitions of the core of database structures, according to the regions superimposable in homologs with known structures, has been show to reduce false negatives in threading predictions. Combination of contact potentials with sequence-motif scores was also shown to increases sensitivity in difficult recognition problems. Use of rigorous p-value calculations was shown to reduce false positives. With these improvements fold recognition may be expected to reliably detect a greater proportion of the distant evolutionary relationships. This has been demonstrated at the 1998 CASP3 workshop, where the NCBI team was awarded first place in fold recognition, among over 90 international groups entering the competition. - protein threading fold recognition structure prediction - Neither Human Subjects nor Human Tissues