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PDB‐scale analysis of known and putative ligand‐binding sites with structural sketches
Author(s) -
Ito JunIchi,
Tabei Yasuo,
Shimizu Kana,
Tomii Kentaro,
Tsuda Koji
Publication year - 2012
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.23232
Subject(s) - structural genomics , protein data bank (rcsb pdb) , computational biology , annotation , pairwise comparison , computer science , similarity (geometry) , representation (politics) , structural alignment , binding site , structural bioinformatics , theoretical computer science , sequence alignment , protein structure , biology , artificial intelligence , genetics , peptide sequence , biochemistry , gene , political science , law , image (mathematics) , politics
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.