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      CAVER: a new tool to explore routes from protein clefts, pockets and cavities

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          Abstract

          Background

          The main aim of this study was to develop and implement an algorithm for the rapid, accurate and automated identification of paths leading from buried protein clefts, pockets and cavities in dynamic and static protein structures to the outside solvent.

          Results

          The algorithm to perform a skeleton search was based on a reciprocal distance function grid that was developed and implemented for the CAVER program. The program identifies and visualizes routes from the interior of the protein to the bulk solvent. CAVER was primarily developed for proteins, but the algorithm is sufficiently robust to allow the analysis of any molecular system, including nucleic acids or inorganic material. Calculations can be performed using discrete structures from crystallographic analysis and NMR experiments as well as with trajectories from molecular dynamics simulations. The fully functional program is available as a stand-alone version and as plug-in for the molecular modeling program PyMol. Additionally, selected functions are accessible in an online version.

          Conclusion

          The algorithm developed automatically finds the path from a starting point located within the interior of a protein. The algorithm is sufficiently rapid and robust to enable routine analysis of molecular dynamics trajectories containing thousands of snapshots. The algorithm is based on reciprocal metrics and provides an easy method to find a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It can also be applied to many other molecules. CAVER is freely available from the web site http://loschmidt.chemi.muni.cz/caver/.

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          Most cited references 33

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          Algorithm 97: Shortest path

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            Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites.

            Identifying the location of ligand binding sites on a protein is of fundamental importance for a range of applications including molecular docking, de novo drug design and structural identification and comparison of functional sites. Here, we describe a new method of ligand binding site prediction called Q-SiteFinder. It uses the interaction energy between the protein and a simple van der Waals probe to locate energetically favourable binding sites. Energetically favourable probe sites are clustered according to their spatial proximity and clusters are then ranked according to the sum of interaction energies for sites within each cluster. There is at least one successful prediction in the top three predicted sites in 90% of proteins tested when using Q-SiteFinder. This success rate is higher than that of a commonly used pocket detection algorithm (Pocket-Finder) which uses geometric criteria. Additionally, Q-SiteFinder is twice as effective as Pocket-Finder in generating predicted sites that map accurately onto ligand coordinates. It also generates predicted sites with the lowest average volumes of the methods examined in this study. Unlike pocket detection, the volumes of the predicted sites appear to show relatively low dependence on protein volume and are similar in volume to the ligands they contain. Restricting the size of the pocket is important for reducing the search space required for docking and de novo drug design or site comparison. The method can be applied in structural genomics studies where protein binding sites remain uncharacterized since the 86% success rate for unbound proteins appears to be only slightly lower than that of ligand-bound proteins. Both Q-SiteFinder and Pocket-Finder have been made available online at http://www.bioinformatics.leeds.ac.uk/qsitefinder and http://www.bioinformatics.leeds.ac.uk/pocketfinder
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              On a routing problem

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                Author and article information

                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                2006
                22 June 2006
                : 7
                : 316
                Affiliations
                [1 ]National Center for Biomolecular Research, Masaryk University, Kamenice 5/A4, 625 00 Brno, Czech Republic
                [2 ]Department of Physical Chemistry and Center for Biomolecules and Complex Molecular Systems, Palacký University, tř. Svobody 26, 771 46 Olomouc, Czech Republic
                [3 ]Loschmidt Laboratories, Masaryk University, Kamenice 5/A4, 625 00 Brno, Czech Republic
                Article
                1471-2105-7-316
                10.1186/1471-2105-7-316
                1539030
                16792811
                Copyright © 2006 Petřek et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Software

                Bioinformatics & Computational biology

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