Vyas Jay, Nowling Ronald J, Maciejewski Mark W, Rajasekaran Sanguthevar, Gryk Michael R, Schiller Martin R
Department of Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, Farmington, CT 06030-3305 USA.
BMC Genomics. 2009 Aug 5;10:360. doi: 10.1186/1471-2164-10-360.
One of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of related data elements. With these two purposes in mind, the authors provide a proposed syntax for minimotif semantics primarily useful for functional annotation.
Herein, we present a structured syntax of minimotifs and their functional annotation. A syntax-based model of minimotif function with established minimotif sequence definitions was implemented using a relational database management system (RDBMS). To assess the usefulness of our standardized semantics, a series of database queries and stored procedures were used to classify SH3 domain binding minimotifs into 10 groups spanning 700 unique binding sequences.
Our derived minimotif syntax is currently being used to normalize minimotif covalent chemistry and functional definitions within the MnM database. Analysis of SH3 binding minimotif data spanning many different studies within our database reveals unique attributes and frequencies which can be used to classify different types of binding minimotifs. Implementation of the syntax in the relational database enables the application of many different analysis protocols of minimotif data and is an important tool that will help to better understand specificity of minimotif-driven molecular interactions with proteins.
在过去几十年里，生物信息学领域最重要的进展之一是观察到短线性肽序列（最小模体）介导了许多类细胞功能，如蛋白质-蛋白质相互作用、分子运输和翻译后修饰。作为一个对最小模体进行编目的数据库（最小模体挖掘器）的创建者和管理者，作者对最小模体众多功能作用的共性有着独特的见解。在允许各种生物信息学资源之间轻松交换数据以及相关数据元素集的内部聚类方面，标准化功能注释显然是有用的。出于这两个目的，作者提供了一种主要用于功能注释的最小模体语义提议语法。
在此，我们展示了最小模体及其功能注释的结构化语法。使用关系数据库管理系统（RDBMS）实现了具有既定最小模体序列定义的基于语法的最小模体功能模型。为了评估我们标准化语义的有用性，使用了一系列数据库查询和存储过程将SH3结构域结合最小模体分类为跨越700个独特结合序列的10组。
我们推导的最小模体语法目前正用于规范MnM数据库中的最小模体共价化学和功能定义。对我们数据库中许多不同研究的SH3结合最小模体数据的分析揭示了可用于对不同类型结合最小模体进行分类的独特属性和频率。在关系数据库中实现该语法能够应用许多不同的最小模体数据分析协议，并且是一个有助于更好地理解最小模体驱动的与蛋白质分子相互作用特异性的重要工具。
