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Resolving protein structure-function-binding site relationships from a binding site similarity network perspective

Mudgal, Richa and Srinivasan, Narayanaswamy and Chandra, Nagasuma (2017) Resolving protein structure-function-binding site relationships from a binding site similarity network perspective. In: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 85 (7). pp. 1319-1335.

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Official URL: http://dx.doi.org/10.1002/prot.25293

Abstract

Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non-homologous protein families, leading to mis-annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold-function relationships at a finer level and with higher confidence. A comprehensive database of 2,020 fold-function-binding site relationships has been systematically generated. A network-based approach is employed to capture the complexity in these relationships, from which different types of associations are deciphered, that identify versatile protein folds performing diverse functions, same function associated with multiple folds and one-to-one relationships. Binding site similarity networks integrated with fold, function, and ligand similarity information are generated to understand the depth of these relationships. Apart from the observed continuity in the functional site space, network properties of these revealed versatile families with topologically different or dissimilar binding sites and structural families that perform very similar functions. As a case study, subtle changes in the active site of a set of evolutionarily related superfamilies are studied using these networks. Tracing of such similarities in evolutionarily related proteins provide clues into the transition and evolution of protein functions. Insights from this study will be helpful in accurate and reliable functional annotations of uncharacterized proteins, poly-pharmacology, and designing enzymes with new functional capabilities. Proteins 2017; 85:1319-1335. (c) 2017 Wiley Periodicals, Inc.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Molecular Biophysics Unit
Division of Physical & Mathematical Sciences > Mathematics
Depositing User: Id for Latest eprints
Date Deposited: 15 Jul 2017 04:28
Last Modified: 15 Jul 2017 04:28
URI: http://eprints.iisc.ac.in/id/eprint/57367

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