Finding Protein Sequence Motifs--methods And Application

在过去的几年中，基因组序列和蛋白质结构的快速积累与序列数据库搜索方法的重大进展是并行的。NCBI开发的功能强大的位置特异性迭代BLAST （PSI-BLAST）方法为我们的蛋白质基序分析工作奠定了基础。开发了一种新的PSI-BLAST应用模式，该模式包括通过重复PSI-BLAST迭代来穷尽数据库搜索以收敛新鉴定的蛋白质家族成员，并在自动过程中实现。另外两个新程序，IMPALA和RPS-BLAST允许人们通过使用单个蛋白质序列作为查询来搜索蛋白质家族谱库。BLAST- clust程序是利用BLAST搜索结果作为输入，通过序列相似性灵活地对蛋白质进行聚类。这些方法被应用于对完全测序的基因组进行系统调查，并产生蛋白质结构折叠的普查。对蛋白质折叠数和家族数的预测进行了理论研究；前者估计约有1000人，后者估计约有5000人。详细分析了几种类型的蛋白质结构域的进化史和种系分布，包括参与RNA代谢和细胞程序性死亡的各种蛋白质，以及大量的gtp酶和相关的atp酶。

In the last few years, rapid accumulation of genome sequences and protein structures has been paralleled by major advances in sequence database search methods. The powerful Position-Specific Iterating BLAST (PSI-BLAST) method developed at the NCBI formed the basis of our work on protein motif analysis. A new mode of PSI-BLAST application which includes exhaustive database search by repeating PSI-BLAST iterations to convergence with newly identified protein family members was developed and implemented in an automatic procedure. Two other new procedures, IMPALA and RPS-BLAST allow one to search a library of protein family profiles by using an individual protein sequence as a query. The BLAST-CLUST procedure was developed to flexibly cluster proteins by sequence similarity using BLAST search outputs in the input. These methods were applied to perform a systematic survey of completely sequenced genomes and to produce a census of protein structural folds. A theoretical study on prediction of the total number of protein folds and families was performed; the estimates of approximately 1000 for the former and approximately 5000 for the latter were produced. The evolutionary history and phyletic distribution of several types of protein domains were analyzed in detail, including a variety of proteins involved in RNA metabolism and programmed cell death as well as the vast class of GTPases and related ATPases.