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. 2009 Aug 5;10:360.
doi: 10.1186/1471-2164-10-360.

A Proposed Syntax for Minimotif Semantics, Version 1

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Free PMC article

A Proposed Syntax for Minimotif Semantics, Version 1

Jay Vyas et al. BMC Genomics. .
Free PMC article

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

Figures

Figure 1
Figure 1
Entity-relationship diagram of a conceptual minimotif data model. Activities are colored orange; relationships are gray; molecules are cyan. There are properties of a Motif/Activity/Target in the database that are not present in this conceptual diagram.
Figure 2
Figure 2
A physical implementation of the conceptual minimotif data model in MySQL. Relationships between tables are indicated. Three convergent lines pointing outward from a table indicate its dependency on another table. A circle or bar at the end of a line indicates that a relationship is optional or mandatory, respectively.
Figure 3
Figure 3
SH3 binding minimotif family. SH3 binding minimotifs were grouped into the 10 minimotif categories using the relational database and Shannon Information Content similarity metric. Surface plots of structures identified for 8 of the 10 group (1ZSG, black; 1NM7, pink; 1AZE, cyan; 2BZ8, blue; 1CKA, magenta; 1OPL, red; 1RLQ orange; 1H3H, green; 1NYG, brown) are shown. The carbon backbones of SH3 domains were fit using Molmol with residues in the β1 and β4 sheets, and the 3-10 helix, to an RMSD of 0.9 [33]. An overlay of each SH3 domain carbon backbone with its peptide minimotif is color matched and relevant minimotif side chain bonds are represented as thickened lines; the surface plot for the overlay is derived from the 1ZSG structure). Structures of the ligands for the RKxxYxxY and WxxxFxxLE minimotifs are not known, but the binding sites on the SH3 domains derived from NMR chemical shift mapping experiments are indicated. RxxPxxP and PxxxPR minimotifs show structures with the peptides in opposing orientations. The consensus sequences (C), total number of minimotifs for C (M), and percentage of potentially ambiguous ligand instances (A) in the MnM 2 database are indicated.

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