ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: Implications for three-dimensional modeling

Bhaskara, Ramachandra M and Padhi, Amrita and Srinivasan, Narayanaswamy (2014) Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: Implications for three-dimensional modeling. In: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 82 (7). pp. 1219-1234.

[img] PDF
pro_str_fun_bio_82-7_1219_2014.pdf - Published Version
Restricted to Registered users only

Download (858kB) | Request a copy
Official URL: http://dx.doi.org/10.1002/prot.24486

Abstract

With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naive Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (approximate to 85%) and specific (approximate to 95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. Proteins 2014; 82:1219-1234. (c) 2013 Wiley Periodicals, Inc.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords: interface evolution; difference domain architecture; differential residue conservation; naive Bayesian classifier; knowledge-based docking
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 22 Jul 2014 11:56
Last Modified: 22 Jul 2014 11:56
URI: http://eprints.iisc.ac.in/id/eprint/49508

Actions (login required)

View Item View Item