Finding Protein Sequence Motifs--methods And Application

寻找蛋白质序列基序--方法与应用

• 批准号: 6681337
• 负责人: Eugene V Koonin
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6681337
• 关键词: abstracting; computer assisted sequence analysis; computer system design /evaluation; protein sequence; statistics /biometry

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.

在过去的几年里，基因组序列和蛋白质结构的快速积累已经被序列数据库搜索方法的重大进展所取代。NCBI开发的强大的位置特异性迭代BLAST（PSI-BLAST）方法构成了我们蛋白质基序分析工作的基础。PSI-BLAST应用程序的一种新模式，其中包括通过重复PSI-BLAST迭代进行穷举数据库搜索，以与新鉴定的蛋白质家族成员收敛，并在自动程序中实现。另外两个新的程序，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。开发了BLAST-CLUST程序，以在输入中使用BLAST搜索输出通过序列相似性灵活地聚类蛋白质。这些方法被应用于执行一个完整的测序基因组的系统调查，并产生一个普查的蛋白质结构折叠。对蛋白质折叠和家族总数的预测进行了理论研究;前者的估计值约为1000，后者约为5000。详细分析了几种类型的蛋白质结构域的进化历史和系统分布，包括参与RNA代谢和程序性细胞死亡的各种蛋白质以及大量的GTP酶和相关ATP酶。