Protein Structure and Function. Application of Bioinformatics Methods - John Rigden 2014

Examples: prediction of the function of structures obtained in structural genomics projects
Collaborative Annotation

Unfortunately, A large number of protein structures solved in structural Genomics projects are not matched by a similarly large number of publications. In fact, publishing a Structure is currently seen as one of the major bottlenecks in the streamlined pipeline of high-throughput structure determination (Rigden 2006). This is not due to a lack of interest in publishing, poor protein Selection, or uninteresting structures. Rather, it suggests that many projects lack such an essential stage as the rapid publication of their results and making them publicly accessible. Consequently, predicting or experimentally determining function—a process that is often time-consuming—takes place after the structure becomes available, frequently in collaboration with other laboratories specializing in the specific protein under study. One way to remedy this situation is to reduce the time spent on these experiments by developing high-throughput assays for screening enzymatic activity (Kuznetsova et al. 2005). Although such assays have proven successful (Proudfoot et al. 2004), limitations associated with implementing certain key enzymatic reactions mean that this approach cannot yet be universally expanded to determine any function. Another approach to improving the annotation of structural genomics targets is to explore the possibility of community annotation of these Proteins using wiki technology (Giles 2007; Mons et al. 2008).

One of the earliest attempts to implement this approach was the TOPSAN project (The Open Cell/13.html">Protein Structure Annotation Network), initiated at the Joint Center for Structural Genomics (JCSG). It currently integrates data for structures generated by the Midwest Center for Structural Genomics (MCSG) and the New York Structural GenomiX Research Center (NYSGXRC). Based on wiki technology (http://www.topsan.org/), the project is viewable by any user, though editing is restricted to registered contributors. The underlying concept of TOPSAN is that collaborative annotation by a global community of experts, each specializing in their specific field, can provide much more comprehensive information on all available proteins with known structures than could ever be achieved by an individual specialist or a small research group. The annotation pages thus offer the general public a combination of automated and expert-curated annotations. The initial version has evolved beyond a prototype and is now expanding to encompass all targets from the Protein Structure Initiative (PSI).

A larger-scale project is PDBWiki (http://pdbwiki.org/), launched in August 2007 by the Structural Proteomics Group at the Max Planck Institute for Molecular Genetics. Currently, the project covers all structures in the PDB database, with each page providing basic protein information alongside links to other Databases and various tools for sequence and structure analysis.

The next step was a new wiki-based encyclopedia utilizing the PDB database, named Proteopedia (http://www.proteopedia.org/). The primary goal of this encyclopedia is to present Structural and functional information about macromolecules in a format easily accessible to students, researchers, and the general public. Each PDB structure has its own dedicated page, populated using data from the OCA database (Prilusky 1996) and other sources. There are several significant differences between Proteopedia and PDBWiki, the most important being a unique in-text linking system to scenes created within the Jmol viewer applet (Proteopedia provides a fully interactive protein structure representation rather than a static one). Using this system, any page editor can easily generate scenes to highlight key protein regions or focus the view on the specific area discussed in the text. This elevates Proteopedia beyond a mere collection of static information pages, introducing an additional layer of interactivity that can be leveraged to vividly illustrate concepts and highlight interesting structural features. Another unique feature of the site is the absence of anonymous edits, with the contributor's full name permanently recorded in the page history. This approach offers a further advantage: users can have areas within the system that are viewable but not editable. This enables the creation of thematic or exemplary articles that remain static, making them suitable for both educational purposes and community annotation.