In recent years, there has been a considerable interest in examining the structure and dynamics of complex networks. Proteins in 3D space may also be considered as complex systems emerged through the interactions of their constituent amino acids. This representation provides a powerful framework to uncover the general organized principle of protein contact network. Here we reviewed protein contact map in terms of protein structure prediction and analyses. In addition, we had also discussed the various computational techniques for the prediction of protein contact maps and the tools to visualize contact maps.

Arnold Emerson I

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Amala A.

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Physica A: Statistical Mechanics and its Applications

The representation of proteins as networks of interacting amino acids, referred to as protein contact networks (PCN), and their subsequent analyses using graph theoretic tools, can provide novel insights into the key functional roles of specific groups of residues. We have characterized the networks corresponding to the native states of 66 proteins (belonging to different families) in terms of their core–periphery organization. The resulting hierarchical classification of the amino acid constituents of a protein arranges the residues into successive layers – having higher core order – with increasing connection density, ranging from a sparsely linked periphery to a densely intra-connected core (distinct from the earlier concept of protein core defined in terms of the three-dimensional geometry of the native state, which has least solvent accessibility). Our results show that residues in the inner cores are more conserved than those at the periphery. Underlining the functional importance of the network core, we see that the receptor sites for known ligand molecules of most proteins occur in the innermost core. Furthermore, the association of residues with structural pockets and cavities in binding or active sites increases with the core order. From mutation sensitivity analysis, we show that the probability of deleterious or intolerant mutations also increases with the core order. We also show that stabilization centre residues are in the innermost cores, suggesting that the network core is critically important in maintaining the structural stability of the protein. A publicly available Web resource for performing core–periphery analysis of any protein whose native state is known has been made available by us at <a href="http://www.imsc.res.in/~sitabhra/proteinKcore/index.html">http://www.imsc.res.in/~sitabhra/proteinKcore/index.html </a>.

Journal of Biosciences

Analysis of core–periphery organization in protein contact networks reveals groups of structurally and functionally critical residues

Topological determinants of the protein structures can be obtained by modeling them as undirected network, which may relate to functionally important residues. In this study, we aim to analyze the Bovine rhodopsin structure (PDB ID: 1U19A) a GPCR family protein. We modeled the protein structure as, an undirected network and network parameters were calculated and compared with the control random networks. Our findings show that the protein contact network possesses a small world property. The functionally important residues in the protein contact network were identified using residue centrality. The statistical significance of the central residues was determined using the Z-score values of the residue centrality. Results show that residues with high Z-score values are highly conserved, are in close proximity with the ligand and are also situated closer to the centre of mass of the protein.

Trends in Bioinformatics

Detection of Active Site Residues in Bovine Rhodopsin Using Network Analysis

Most studies have shown that globular proteins exist in small-world networks. The present study is an attempt to determine differences in network parameters between transmembrane and globular proteins. Each protein is represented as an undirected graph, where residues represent nodes and inter-residue interactions as the edges. This was then compared to the degree-preserved random controls, to observe if any variation existed. Results indicate that there is a significant difference in shortest path lengths between transmembrane and globular proteins. Hydrophobic amino acids were found to be more spatially distributed in the transmembrane than in globular proteins causing significantly higher values of shortest path lengths (<math xmlns="http://www.w3.org/1998/Math/MathML"><mi is="true">L</mi></math>). Assortativity values too, were found to be significantly higher in the transmembrane than in globular proteins which is due to the highly connected amino acid residues being exposed to the solvent in transmembrane proteins. On analyzing the closeness centrality, it was found that globular proteins have significantly higher values than the transmembrane proteins. We therefore conclude that transmembrane proteins possess small-world characteristics similar to that of globular proteins.

Network analysis of transmembrane protein structures

Transmembrane proteins serve as receptors, transporters or as enzymes. They mediate a broad range of fundamental cellular activities including signal transduction, cell trafficking and photosynthesis. In this study, we analyzed the significance of central residues in the polytopic transmembrane proteins. Each protein is represented as an undirected graph, where residues represent nodes and inter-residue interactions as the edges. Residue centrality was calculated by removing the nodes and its corresponding edges from the protein contact network. Results revealed that 80% of the predicted central residues had normalized conservation values below the mean since they were slowly evolving conserved sites. We also found that 56% of amino acids were interacting with the ligand molecules and metal ions. Predicted central residues in the polytopic transmembrane proteins were found to account for 84% of binding and active site amino acids. From mutation sensitivity analysis, it was observed that 89% of central residues had deleterious mutations whose probabilities were greater than their mean value. Interestingly, we find that z-score values of each amino acid positively correlate with the conservation scores and also with the degrees of each node. Results show that 87% of central residues are hub residues.

Journal	Data powered by TypesetPhysica A: Statistical Mechanics and its Applications
Publisher	Data powered by TypesetElsevier BV
ISSN	0378-4371
Open Access	0