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Open Access Highly Accessed Research article

Visualisation and graph-theoretic analysis of a large-scale protein structural interactome

Dan Bolser2, Panos Dafas1, Richard Harrington2, Jong Park23 and Michael Schroeder1*

Author Affiliations

1 Department of Computing, City University, London EC1V 0HB, UK

2 Dunn Human Nutrition Unit, Medical Research Council, Cambridge CB2 2XY, UK

3 Department of BioSystems, Korea Advanced Institute of Science and Technology, Korea

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BMC Bioinformatics 2003, 4:45  doi:10.1186/1471-2105-4-45

Published: 8 October 2003

Abstract

Background

Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network.

Results

We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network.

Conclusions

Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.

Keywords:
Structural Interactome; Protein Interaction; Interactomics; Graph-theory; Interaction Rank; Taxonomic Diversity; PSIEYE; PSIMAP.