From Workstations to Workbenches: Towards Predicting Physicochemically Viable Protein-Protein Interactions Across a Host and a Pathogen

Ramakrishnan, Gayatri and Chandra, Nagasuma R and Srinivasan, Narayanaswamy (2014) From Workstations to Workbenches: Towards Predicting Physicochemically Viable Protein-Protein Interactions Across a Host and a Pathogen. In: IUBMB LIFE, 66 (11). pp. 759-774.

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Abstract

The understanding of protein-protein interactions is indispensable in comprehending most of the biological processes in a cell. Small-scale experiments as well as large-scale high-throughput techniques over the past few decades have facilitated identification and analysis of protein-protein interactions which form the basis of much of our knowledge on functional and regulatory aspects of proteins. However, such rich catalog of interaction data should be used with caution when establishing protein-protein interactions in silico, as the high-throughput datasets are prone to false positives. Numerous computational means developed to pursue genome-wide studies on protein-protein interactions at times overlook the mechanistic and molecular details, thus questioning the reliability of predicted protein-protein interactions. We review the development, advantages, and shortcomings of varied approaches and demonstrate that by providing a structural viewpoint in terms of shape complementarity and interaction energies at protein-protein interfaces coupled with information on expression and localization of proteins homologous to an interacting pair, it is possible to assess the credibility of predicted interactions in biological context. With a focus on human pathogen Mycobacterium tuberculosis H37Rv, we show that such scrupulous use of details at the molecular level can predict physicochemically viable protein-protein interactions across host and pathogen. Such predicted interactions have the potential to provide molecular basis of probable mechanisms of pathogenesis and hence open up ways to explore their usefulness as targets in the light of drug discovery. (c) 2014 IUBMB Life, 66(11):759-774, 2014

Item Type:	Journal Article
Publication:	IUBMB LIFE
Publisher:	WILEY-BLACKWELL
Additional Information:	Copy right for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords:	homology-based approaches; host-pathogen interactions; Mycobacterium tuberculosis; protein-protein interactions
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Biological Sciences > Molecular Biophysics Unit Division of Physical & Mathematical Sciences > Mathematics
Date Deposited:	24 Feb 2015 05:53
Last Modified:	24 Feb 2015 05:53
URI:	http://eprints.iisc.ac.in/id/eprint/50860

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