Real-time structural motif searching in proteins using an inverted index strategy.
Real-time structural motif searching in proteins using an inverted index strategy.
复制标题
使用倒数索引策略在蛋白质中进行实时结构基序搜索。
DOI：
10.1371/journal.pcbi.1008502
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发表时间：
2020-12
影响因子：
4.3
通讯作者：
Rose AS
中科院分区：
文献类型：
--
作者：
Bittrich S;Burley SK;Rose AS
蛋白质的生物化学和生物学功能是多肽链整体折叠的产物，并且通常是由较少数量的氨基酸组成的结构基序的产物，所述氨基酸构成催化中心或在氨基酸序列中可能彼此远离的结合位点。检测这种结构基序可以提供有价值的见解，以前未表征的蛋白质的功能。从技术上讲，这仍然是一个极具挑战性的问题，因为蛋白质数据库（PDB）存档的大小。现有的方法依赖于通过序列相似性的聚类，并且可能在计算上很慢。我们开发了一种新方法，该方法使用倒排索引策略，能够以无与伦比的速度分析> 170，000个PDB结构。倒排索引方法的效率关键取决于识别包含查询基序的少量结构，并忽略大多数不相关的结构。我们的方法（实现在motif.rcsb.org），使实时检索和叠加的结构图案，无论是从参考结构提取或上传的用户。在这里，我们描述了该方法，并提出了五个案例研究，验证其效率和速度分析蛋白质和核酸的三维结构。蛋白质数据库（PDB）提供了超过170，000个蛋白质，核酸和生物复合物的三维结构的开放访问。PDB结构之间的相似性提供了有价值的功能和进化的见解，但这种相似性在序列或全局结构水平上可能并不明显。在整个数据库中，有重复出现的结构基序-例如，支持催化活性的适当数量的邻近残基的组。共同结构基序的鉴定可以揭示蛋白质之间的相似性，并作为氨基酸空间构型的指纹，例如丝氨酸蛋白酶中发现的His-Asp-Ser催化三联体或锌指DNA结合结构域中发现的锌配位位点。我们提出了一种高效而灵活的策略，允许用户第一次在整个PDB档案中实时搜索任意结构基序。我们的方法随着沉积结构的数量和复杂性的增加而有利地扩展，并且还具有适用于大分子背景下的其他应用的潜力。
Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids. The Protein Data Bank (PDB) provides open access to more than 170,000 three-dimensional structures of proteins, nucleic acids, and biological complexes. Similarities between PDB structures give valuable functional and evolutionary insights but such resemblance may not be evident at sequence or global structure level. Throughout the database, there are recurring structural motifs—groups of modest numbers of residues in proximity that, for example, support catalytic activity. Identification of common structural motifs can reveal similarities between proteins and serve as fingerprints for spatial configurations of amino acids, such as the His-Asp-Ser catalytic triad found in serine proteases or the zinc coordination site found in Zinc Finger DNA-binding domains. We present a highly efficient yet flexible strategy that allows users for the first time to search for arbitrary structural motifs across the entire PDB archive in real-time. Our approach scales favorably with the increasing number and complexity of deposited structures, and, also, has the potential to be adapted for other applications in a macromolecular context.
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影响因子：
1.7
作者：
Chen, Brian Y.;Fofanov, Viacheslav Y.;Kavraki, Lydia E.
通讯作者：
Kavraki, Lydia E.
影响因子：
3
作者：
Liu, Pu;Agrafiotis, Dimitris K.;Theobald, Douglas L.
通讯作者：
Theobald, Douglas L.
影响因子：
2.9
作者：
Meng, EC;Polacco, BJ;Babbitt, PC
通讯作者：
Babbitt, PC
DOI：
10.1073/pnas.88.23.10495
发表时间：
1991-12-01
影响因子：
11.1
作者：
NUSSINOV, R;WOLFSON, HJ
通讯作者：
WOLFSON, HJ
影响因子：
5.8
作者：
Rose, Alexander S.;Bradley, Anthony R.;Rose, Peter W.
通讯作者：
Rose, Peter W.