ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins

ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins

2007 | Markus Wiederstein and Manfred J. Sippl
ProSA-web is an interactive web service for the recognition of errors in three-dimensional structures of proteins. It is an extension of the classic ProSA program, which is widely used for checking 3D models of protein structures for potential errors. ProSA-web provides a user-friendly interface that allows users to analyze protein structures by displaying scores and energy plots that highlight potential problems. The service compares the quality scores of a protein with those of all known protein structures and highlights problematic parts of a structure in a 3D molecule viewer. ProSA-web is particularly useful for the validation of protein structures obtained from X-ray analysis, NMR spectroscopy, and theoretical calculations. The service requires the atomic coordinates of the model to be evaluated. Users can supply coordinates either by uploading a file in PDB format or by entering the four-letter code of a protein structure available from PDB. A chain identifier and an NMR model number may be used to specify a particular model. The computational engine used for the calculation of scores and plots is standard ProSA, which uses knowledge-based potentials of mean force to evaluate model accuracy. All calculations are carried out with Cα potentials, hence ProSA-web can also be applied to low-resolution structures or other cases where the Cα trace is available only. The z-score indicates overall model quality and measures the deviation of the total energy of the structure with respect to an energy distribution derived from random conformations. Z-scores outside a range characteristic for native proteins indicate erroneous structures. The energy plot shows the local model quality by plotting energies as a function of amino acid sequence position. In general, positive values correspond to problematic or erroneous parts of a model. The 3D structure of the protein is visualized using the molecule viewer Jmol, which allows users to explore the structure in more detail. ProSA-web is used to validate protein structures by comparing them with known structures. In a typical example, the structure of MsbA from Escherichia coli was found to be incorrect, and the related publication had to be retracted. ProSA-web results showed extreme deviations for the incorrect structure, while the recently released structure of Sav1866 showed features characteristic for native structures. This demonstrates that ProSA-web is an effective tool for identifying errors in protein structures.ProSA-web is an interactive web service for the recognition of errors in three-dimensional structures of proteins. It is an extension of the classic ProSA program, which is widely used for checking 3D models of protein structures for potential errors. ProSA-web provides a user-friendly interface that allows users to analyze protein structures by displaying scores and energy plots that highlight potential problems. The service compares the quality scores of a protein with those of all known protein structures and highlights problematic parts of a structure in a 3D molecule viewer. ProSA-web is particularly useful for the validation of protein structures obtained from X-ray analysis, NMR spectroscopy, and theoretical calculations. The service requires the atomic coordinates of the model to be evaluated. Users can supply coordinates either by uploading a file in PDB format or by entering the four-letter code of a protein structure available from PDB. A chain identifier and an NMR model number may be used to specify a particular model. The computational engine used for the calculation of scores and plots is standard ProSA, which uses knowledge-based potentials of mean force to evaluate model accuracy. All calculations are carried out with Cα potentials, hence ProSA-web can also be applied to low-resolution structures or other cases where the Cα trace is available only. The z-score indicates overall model quality and measures the deviation of the total energy of the structure with respect to an energy distribution derived from random conformations. Z-scores outside a range characteristic for native proteins indicate erroneous structures. The energy plot shows the local model quality by plotting energies as a function of amino acid sequence position. In general, positive values correspond to problematic or erroneous parts of a model. The 3D structure of the protein is visualized using the molecule viewer Jmol, which allows users to explore the structure in more detail. ProSA-web is used to validate protein structures by comparing them with known structures. In a typical example, the structure of MsbA from Escherichia coli was found to be incorrect, and the related publication had to be retracted. ProSA-web results showed extreme deviations for the incorrect structure, while the recently released structure of Sav1866 showed features characteristic for native structures. This demonstrates that ProSA-web is an effective tool for identifying errors in protein structures.
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