RMB generated and worked on Figures , Tables and all Supporting Information. AP helped generate Supporting Information Figures S1 and S2 and curate datasets. RMB and NS conceived and designed the study and also wrote the article.
Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: Implications for three-dimensional modeling
Article first published online: 6 DEC 2013
© 2013 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 82, Issue 7, pages 1219–1234, July 2014
How to Cite
Bhaskara, R. M., Padhi, A. and Srinivasan, N. (2014), Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: Implications for three-dimensional modeling. Proteins, 82: 1219–1234. doi: 10.1002/prot.24486
- Issue published online: 11 JUN 2014
- Article first published online: 6 DEC 2013
- Accepted manuscript online: 26 NOV 2013 12:07AM EST
- Manuscript Accepted: 19 NOV 2013
- Manuscript Revised: 4 NOV 2013
- Manuscript Received: 19 JUN 2013
- Council of Scientific and Industrial Research (CSIR), India (to RMB), Kishore Vaigyanik Protsahan Yojana (KVPY), IISc (to AP), and Mathematical Biology programme from Department of Science and Technology, India as well as by Department of Biotechnology, India
- interface evolution;
- difference domain architecture;
- differential residue conservation;
- naïve Bayesian classifier;
- knowledge-based docking
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 naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼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. © 2013 Wiley Periodicals, Inc.