PDB-scale analysis of known and putative ligand-binding sites with structural sketches
Jun-Ichi Ito
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8568, Japan
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
Search for more papers by this authorYasuo Tabei
Minato Discrete Structure Manipulation System Project, ERATO, Japan Science and Technology Agency, Sapporo 060-0814, Japan
Search for more papers by this authorKana Shimizu
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
Search for more papers by this authorCorresponding Author
Kentaro Tomii
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8568, Japan
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan===Search for more papers by this authorKoji Tsuda
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
Minato Discrete Structure Manipulation System Project, ERATO, Japan Science and Technology Agency, Sapporo 060-0814, Japan
Search for more papers by this authorJun-Ichi Ito
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8568, Japan
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
Search for more papers by this authorYasuo Tabei
Minato Discrete Structure Manipulation System Project, ERATO, Japan Science and Technology Agency, Sapporo 060-0814, Japan
Search for more papers by this authorKana Shimizu
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
Search for more papers by this authorCorresponding Author
Kentaro Tomii
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8568, Japan
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan===Search for more papers by this authorKoji Tsuda
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan
Minato Discrete Structure Manipulation System Project, ERATO, Japan Science and Technology Agency, Sapporo 060-0814, Japan
Search for more papers by this authorAbstract
Computational investigation of protein functions is one of the most urgent and demanding tasks in the field of structural bioinformatics. Exhaustive pairwise comparison of known and putative ligand-binding sites, across protein families and folds, is essential in elucidating the biological functions and evolutionary relationships of proteins. Given the vast amounts of data available now, existing 3D structural comparison methods are not adequate due to their computation time complexity. In this article, we propose a new bit string representation of binding sites called structural sketches, which is obtained by random projections of triplet descriptors. It allows us to use ultra-fast all-pair similarity search methods for strings with strictly controlled error rates. Exhaustive comparison of 1.2 million known and putative binding sites finished in ∼30 h on a single core to yield 88 million similar binding site pairs. Careful investigation of 3.5 million pairs verified by TM-align revealed several notable analogous sites across distinct protein families or folds. In particular, we succeeded in finding highly plausible functions of several pockets via strong structural analogies. These results indicate that our method is a promising tool for functional annotation of binding sites derived from structural genomics projects. Proteins 2011. © 2012 Wiley Periodicals, Inc.
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