Abstract
BackgroundProtein structure comparison is one of the most widely performed tasks in bioinformatics. However, currently used methods have problems with the so-called "difficult similarities", including considerable shifts and distortions of structure, sequential swaps and circular permutations. There is a demand for efficient and automated systems capable of overcoming these difficulties, which may lead to the discovery of previously unknown structural relationships.ResultsWe present a novel method for protein structure comparison based on the formalism of local descriptors of protein structure - DEscriptor Defined Alignment (DEDAL). Local similarities identified by pairs of similar descriptors are extended into global structural alignments. We demonstrate the method's capability by aligning structures in difficult benchmark sets: curated alignments in the SISYPHUS database, as well as SISY and RIPC sets, including non-sequential and non-rigid-body alignments. On the most difficult RIPC set of sequence alignment pairs the method achieves an accuracy of 77% (the second best method tested achieves 60% accuracy).ConclusionsDEDAL is fast enough to be used in whole proteome applications, and by lowering the threshold of detectable structure similarity it may shed additional light on molecular evolution processes. It is well suited to improving automatic classification of structure domains, helping analyze protein fold space, or to improving protein classification schemes. DEDAL is available online at http://bioexploratorium.pl/EP/DEDAL.
Highlights
Protein structure comparison is one of the most widely performed tasks in bioinformatics
The reason behind the aforementioned problems is the fact that proteins which are fairly elastic objects are represented by fixed atomic coordinates in 3D space, usually obtained from crystallographic experiments and most methods focus on finding a superposition which would minimize the distance between the respective amino-acids
A local descriptor is a small part of a structure that can be viewed as a residue-attached local environment
Summary
Protein structure comparison is one of the most widely performed tasks in bioinformatics. There exists a growing set of known biologically significant similarities between protein structures with considerable spatial distortions, various segment swaps or circular permutations [2,3,4,5]. These “gold standard” alignments are prepared with substantial human intervention [6] and studies have shown that no automated techniques to date are capable of satisfactorily reproducing them [7]. See a recent review [26]
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