BackgroundMany newly detected point mutations are located in protein-coding regions of the human genome. Knowledge of their effects on the protein's 3D structure provides insight into the protein's mechanism, can aid the design of further experiments, and eventually can lead to the development of new medicines and diagnostic tools.ResultsIn this article we describe HOPE, a fully automatic program that analyzes the structural and functional effects of point mutations. HOPE collects information from a wide range of information sources including calculations on the 3D coordinates of the protein by using WHAT IF Web services, sequence annotations from the UniProt database, and predictions by DAS services. Homology models are built with YASARA. Data is stored in a database and used in a decision scheme to identify the effects of a mutation on the protein's 3D structure and function. HOPE builds a report with text, figures, and animations that is easy to use and understandable for (bio)medical researchers.ConclusionsWe tested HOPE by comparing its output to the results of manually performed projects. In all straightforward cases HOPE performed similar to a trained bioinformatician. The use of 3D structures helps optimize the results in terms of reliability and details. HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

We present a series of databanks (http://swift.cmbi.ru.nl/gv/facilities/) that hold information that is computationally derived from Protein Data Bank (PDB) entries and that might augment macromolecular structure studies. These derived databanks run parallel to the PDB, i.e. they have one entry per PDB entry. Several of the well-established databanks such as HSSP, PDBREPORT and PDB_REDO have been updated and/or improved. The software that creates the DSSP databank, for example, has been rewritten to better cope with π-helices. A large number of databanks have been added to aid computational structural biology; some examples are lists of residues that make crystal contacts, lists of contacting residues using a series of contact definitions or lists of residue accessibilities. PDB files are not the optimal presentation of the underlying data for many studies. We therefore made a series of databanks that hold PDB files in an easier to use or more consistent representation. The BDB databank holds X-ray PDB files with consistently represented B-factors. We also added several visualization tools to aid the users of our databanks.

The Protein Data Bank (PDB) is the world-wide repository of macromolecular structure information. We present a series of databases that run parallel to the PDB. Each database holds one entry, if possible, for each PDB entry. DSSP holds the secondary structure of the proteins. PDBREPORT holds reports on the structure quality and lists errors. HSSP holds a multiple sequence alignment for all proteins. The PDBFINDER holds easy to parse summaries of the PDB file content, augmented with essentials from the other systems. PDB_REDO holds re-refined, and often improved, copies of all structures solved by X-ray. WHY_NOT summarizes why certain files could not be produced. All these systems are updated weekly. The data sets can be used for the analysis of properties of protein structures in areas ranging from structural genomics, to cancer biology and protein design.

The WHAT IF molecular-modelling and drug design program is widely distributed in the world of protein structure bioinformatics. Although originally designed as an interactive application, its highly modular design and inbuilt control language have recently enabled its deployment as a collection of programmatically accessible web services. We report here a collection of WHAT IF-based protein structure bioinformatics web services: these relate to structure quality, the use of symmetry in crystal structures, structure correction and optimization, adding hydrogens and optimizing hydrogen bonds and a series of geometric calculations. The freely accessible web services are based on the industry standard WS-I profile and the EMBRACE technical guidelines, and are available via both REST and SOAP paradigms. The web services run on a dedicated computational cluster; their function and availability is monitored daily.

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Identification of natural compounds, especially secondary metabolites, has been hampered by the lack of easy to use and accessible reference databases. Nuclear magnetic resonance (NMR) spectroscopy is the most selective technique for identification of unknown metabolites. High quality (1)H NMR (proton nuclear magnetic resonance) spectra combined with elemental composition obtained from mass spectrometry (MS) are essential for the identification process. Here, we present MetIDB, a reference database of experimental and predicted (1)H NMR spectra of 6000 flavonoids. By incorporating the stereochemistry, intramolecular interactions, and solvent effects into the prediction model, chemical shifts and couplings were predicted with great accuracy. A user-friendly web-based interface for MetIDB has been established providing various interfaces to the data and data-mining possibilities. For each compound, additional information is available comprising compound annotation, a (1)H NMR spectrum, 2D and 3D structure with correct stereochemistry, and monoisotopic mass as well as links to other web resources. The combination of chemical formula and (1)H NMR chemical shifts proved to be very efficient in metabolite identification, especially for isobaric compounds. Using this database, the process of flavonoid identification can then be significantly shortened by avoiding repetitive elucidation of already described compounds.

Quantifying patterns of adaptive divergence between taxa is a major goal in the comparative and evolutionary study of prokaryote genomes. When applied appropriately, the McDonald-Kreitman (MK) test is a powerful test of selection based on the relative frequency of non-synonymous and synonymous substitutions between species compared to non-synonymous and synonymous polymorphisms within species. The webserver ODoSE (Ortholog Direction of Selection Engine) allows the calculation of a novel extension of the MK test, the Direction of Selection (DoS) statistic, as well as the calculation of a weighted-average Neutrality Index (NI) statistic for the entire core genome, allowing for systematic analysis of the evolutionary forces shaping core genome divergence in prokaryotes. ODoSE is hosted in a Galaxy environment, which makes it easy to use and amenable to customization and is freely available at www.odose.nl.