Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Network Robustness and Modularity of Protein Structures in the Identification of Key Residues for Allosteric Communications
Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flow of information between amino acids. By removal of nodes from the protein network, we identify fold centrally-conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. The agreement between the fold centrally conserved residues and residues experimentally suggested to mediate signaling, further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues whose removal increases the characteristic path length in protein networks, may relate to the system fragility.
Further results show that protein domains consist of modules interconnected by fold-centrally conserved residues. Modules characterize experimentally identified functional regions and based on our results we propose that high modularity modules include functional sites and are the basic functional units. We provide examples (the G subunit and P450 Cytochromes) illustrating that the modular architecture of active sites is linked to their functional specialization.
Antonio del Sol1
1Bioinformatics Research Unit