Residue centrality in alpha helical polytopic 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.

► Residue centrality distributions are homogenous in small world and random networks.
► Z-scores positively correlate with degrees and 87% of central residues are hubs.
► Mutation analysis reveals that central residues contribute to viability of proteins.