PocketMatch: A new algorithm to compare binding sites in protein structures
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- Indian Institute of Science, Bioinformatics Centre and Supercomputer Education and Research Centre
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This manuscript is a preprint. A published version is available at:
10.1186/1471-2105-9-543 (Peer Reviewed) Published in BMC Bioinformatics 2008, 9:543- Document Type:
- Manuscript
- Date:
- Received 21 November 2008 08:59 UTC; Posted 21 November 2008
- Subjects:
- Bioinformatics
- Abstract:
Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented.
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- License:
- This document is licensed to the public under the Creative Commons Attribution 3.0 License
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Kalidas, Yeturu and Chandra, Nagasuma. PocketMatch: A new algorithm to compare binding sites in protein structures. Available from Nature Precedings <http://dx.doi.org/10.1038/npre.2008.2142.2> (2008)
- Version info:
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Published version:
10.1186/1471-2105-9-543 (Peer Reviewed) Published in BMC Bioinformatics 2008, 9:543 -
Other versions of this document in Nature Precedings
Version number Document title Date v1 Posted 01 August 2008 Other versions of this document elsewhere on the web
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