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.