Analysis of core–periphery organization in protein contact networks reveals groups of structurally and functionally critical residues.
Loading...
Date
2015-10
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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 https://www.imsc.res.in/
~sitabhra/proteinKcore/index.html.
Description
Keywords
Core–periphery, hierarchical core decomposition, protein contact network
Citation
Isaac Arnold Emerson, Sinha Sitabhra. Analysis of core–periphery organization in protein contact networks reveals groups of structurally and functionally critical residues. Journal of Biosciences. 2015 Oct; 40(4): 683-699.