Construction and Analysis of Protein-Protein Interaction Network: Role in Identification of Key Signaling Molecules Involved in a Disease Pathway

Construction and Analysis of Protein-Protein Interaction Network: Role in Identification of Key Signaling Molecules Involved in a Disease Pathway

Divya Dasagrandhi, Arul Salomee Kamalabai Ravindran, Anusuyadevi Muthuswamy, Jayachandran K. S.
Copyright: © 2019 |Pages: 17
DOI: 10.4018/978-1-5225-7326-5.ch009
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Understanding the mechanisms of a disease is highly complicated due to the complex pathways involved in the disease progression. Despite several decades of research, the occurrence and prognosis of the diseases is not completely understood even with high throughput experiments like DNA microarray and next-generation sequencing. This is due to challenges in analysis of huge data sets. Systems biology is one of the major divisions of bioinformatics and has laid cutting edge techniques for the better understanding of these pathways. Construction of protein-protein interaction network (PPIN) guides the modern scientists to identify vital proteins through protein-protein interaction network, which facilitates the identification of new drug target and associated proteins. The chapter is focused on PPI databases, construction of PPINs, and its analysis.
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Several decades of research in analyzing the mechanism of a disease progression, still cannot unravel complete signaling pathways. This is due to complexity in the mechanism of signal transduction. Proteins are the complex functional units that plays vital role in cellular metabolism. Proteins interact with other proteins to perform every task involved in cellular protection and death. Interaction of proteins determines the fate and acts molecular machines. Activity of proteins depends on its amino acid sequence, structure, chemical modifications, folding and active sites. All these together makes a protein to perform biochemical reactions and diverse functions based on the surrounding environmental milieu in both cellular and organ system levels. Physiochemical properties of proteins vary based on the levels of expression and localization.

Protein interactions stood for all the biological functions such as DNA replication, transcription, translation, cell division, growth and metabolism (Haque et al., 2018) . It is challenging to identify all the mechanisms and getting a clue about vital proteins that aggravates the pathogenesis of the disease either by in vivo or in vitro experiments as large set of proteins are involved. A critical step was laid in the field of bioinformatics to analyze large set of proteins by constructing Protein-Protein interaction network that helps in decoding molecular basis of a disease and molecular machinery of cells. Identifications of key proteins involved in a disease not only help in understanding disease mechanism but also play a best role in identifying best therapeutic targets for drug discovery with little or no side effects (Ashraf et al., 2018; Tsai et al., 2009).

Protein-Protein Interactions

How a cell decides its biological function? The decision made by cells depends on the coordination of protein interactions. Isolated protein is not functional but more than 80% of proteins interact with other to become functional (Keskin et al., 2016). The different regulatory behavior depends on different pathway interactions based on protein structure, dynamics and conformational change. The synthetic biology elucidates the different behaviors of protein in the complex system.

PPI are defined as the physical interactions between two or more proteins that help to process different functions of the cell. The interactions are either stable or unstable and depend on the environment, signaling from other molecular complexes and time. The interactions of these proteins are either in subcellular or extracellular regions. The complete set of PPI in a cell or an organism is known as interactome. Proteins in the interactome depend on the cell types as expressions of proteins vary in distinct cell types.

The interactions are said to be direct, if there is a molecular contact between two proteins and indirect, if two proteins interact by means of an intermediate (Zhang et al., 2015). Permanent PPI are strong and irreversible and transient PPI are either weak or strong based on oligomeric state (Perkins et al., 2010). Analyzing transient interactions is a challenging task as they are not stable. Fine-tuned technologies are required to analyze these as they have key role in biological network. PPI are not always seen in the same way as the presence of proteins vary based on cellular location, organ, cellular stage, environment, post translational modifications and protein folding. Alterations in these interactions cause disease or malfunction of the metabolic process.

PPI can be determined experimentally by yeast two-hybrid system, Nuclear Magnetic Resonance spectroscopy, co-immuno precipitation and phage display etc. (Rao et al., 2014) But computational analysis of the PPI network can analyze the huge data and helps to understand the role of proteins.

Figure 1.

Various methods to analyze protein-protein interactions using in vivo, in vitro and in silico methods.


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