Network-Based Models as Tools Hinting at Nonevident Protein Functionality

Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey.
Annual Review of Biophysics (Impact Factor: 15.44). 02/2012; 41(1):205-25. DOI: 10.1146/annurev-biophys-050511-102305
Source: PubMed


Network-based models of proteins are popular tools employed to determine dynamic features related to the folded structure. They encompass all topological and geometric computational approaches idealizing proteins as directly interacting nodes. Topology makes use of neighborhood information of residues, and geometry includes relative placement of neighbors. Coarse-grained approaches efficiently predict alternative conformations because of inherent collectivity in the protein structure. Such collectivity is moderated by topological characteristics that also tune neighborhood structure: That rich residues have richer neighbors secures robustness toward random loss of interactions/nodes due to environmental fluctuations/mutations. Geometry conveys the additional information of force balance to network models, establishing the local shape of the energy landscape. Here, residue and/or bond perturbations are critically evaluated to suggest new experiments, as network-based computational techniques prove useful in capturing domain movements and conformational shifts resulting from environmental alterations. Evolutionarily conserved residues are optimally connected, defining a subnetwork that may be utilized for further coarsening.

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    • "The network paradigm has been extensively used to describe structure, topology and dynamics of proteins (Csermely et al., 2013; Atilgan et al., 2012; Vishveshwara et al., 2009; Collier and Ortiz, 2013; Feher et al., 2014). The intramolecular non-covalent interactions in a protein are known to be crucial in determining the protein structure and they can be collectively represented in the form of a network, namely a Protein Structure Network (PSN), where the residues are the nodes of the network connected by edges that depend on their interaction strength. "
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