Sequence‐structure mapping errors in the PDB: OB‐fold domains

Abstract

The Protein Data Bank (PDB) is the single most important repository of structural data for proteins and other biologically relevant molecules. Therefore, it is critically important to keep the PDB data, as much as possible, error-free. In this study, we have analyzed PDB crystal structures possessing oligonucleotide/ oligosaccharide binding (OB)-fold, one of the highly populated folds, for the presence of sequence-structure mapping errors. Using energy-based structure quality assessment coupled with sequence analyses, we have found that there are at least five OB-structures in the PDB that have regions where sequences have been incorrectly mapped onto the structure. We have demonstrated that the combination of these computation techniques is effective not only in detecting sequence-structure mapping errors, but also in providing guidance to correct them. Namely, we have used results of computational analysis to direct a revision of X-ray data for one of the PDB entries containing a fairly inconspicuous sequence-structure mapping error. The revised structure has been deposited with the PDB. We suggest use of computational energy assessment and sequence analysis techniques to facilitate structure determination when homologs having known structure are available to use as a reference. Such computational analysis may be useful in either guiding the sequence-structure assignment process or verifying the sequence mapping within poorly defined regions.Keywords: structure quality assessment; sequence register errors; sequence analysis; molecular modeling; X-ray crystallography; SSB protein; PDB Experimentally determined three-dimensional (3D) structures of proteins are of great importance and of broad interest. The knowledge of protein structures is critical in understanding and/or modifying their molecular function. Structural data are also invaluable in understanding the physical basis of protein folding and stability. Therefore, it is very desirable that 3D structures deposited into the Protein Data Bank (PDB; Berman et al. 2000) are as much as possible free from errors. The PDB structural data are extensively used in a number of derivative databases and in the development of various computational biology approaches, including protein structure prediction methods. Once a flawed protein structure gets into the PDB, it may propagate into other public databases and affect the interpretation of structure-function relationship for the whole protein family.There are a number of methods developed to date for the detection of "unusual" protein structures that are often indicative of structural flaws within specific regions of the protein chain (e.g., Luthy et al. 1992;Laskowski et al. 1993;Sippl 1993;Hooft et al. 1996). However, in most cases when poor structural quality scores are obtained for a short region, it is difficult to judge whether this is because of Article published online ahead of print. Article and publication date are at

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