Expansion of “low complex” repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP—involved in important housekeeping processes—retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling

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Zinc is a new modelling language developed as part of the G12 project. It has four important characteristics. First, Zinc allows specification of models using a natural mathematical-like notation. To do so it supports overloaded functions and predicates and automatic coercion and provides arithmetic, finite domain and set constraints. Second, while Zinc is a relatively simple and small language, it can be readily extended to different application areas by means of powerful language constructs such as user-defined predicates and functions and constrained types. Third, Zinc provides sophisticated type and instantiation checking which allows early detection of errors in models. Finally, perhaps the main novelty in Zinc is that it is designed to support a modelling methodology in which the same conceptual model can be automatically mapped into different design models, thus allowing modellers to easily "plug and play" with different solving techniques and so choose the most 230 Constraints (2008) 13:229-267 appropriate for that problem. We describe in detail the various language features of Zinc and the many trade-offs we faced in its design.

Proteases play a fundamental role in the control of intra-and extracellular processes by binding and cleaving specific amino acid sequences. Identifying these targets is extremely challenging. Current computational attempts to predict cleavage sites are limited, representing these amino acid sequences as patterns or frequency matrices. Here we present PoPS, a publicly accessible bioinformatics tool (http://pops.csse.monash.edu.au/) which provides a novel method for building computational models of protease specificity that, while still being based on these amino acid sequences, can be built from any experimental data or expert knowledge available to the user. PoPS specificity models can be used to predict and rank likely cleavages within a single substrate, and within entire proteomes. Other factors, such as the secondary or tertiary structure of the substrate, can be used to screen unlikely sites. Furthermore, the tool also provides facilities to infer, compare and test models, and to store them in a publicly accessible database.