Protein conformational switch discerned via network centrality properties
| Autor: | Tongye Shen, Bill Pham, David Foutch |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Closeness
Biophysics Biomolecular structure Computational biology Biochemistry 03 medical and health sciences 0302 clinical medicine Protein structure Betweenness centrality Conformational switch Structural Biology Genetics Network centrality ComputingMethodologies_COMPUTERGRAPHICS 030304 developmental biology 0303 health sciences biology Chemistry Protein structure network Computer Science Applications Allosteric enzyme Structural biology 030220 oncology & carcinogenesis biology.protein Network analysis Centrality TP248.13-248.65 Research Article Biotechnology |
| Zdroj: | Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 3599-3608 (2021) Computational and Structural Biotechnology Journal |
| ISSN: | 2001-0370 |
| Popis: | Graphical abstract Network analysis has emerged as a powerful tool for examining structural biology systems. The spatial organization of the components of a biomolecular structure has been rendered as a graph representation and analyses have been performed to deduce the biophysical and mechanistic properties of these components. For proteins, the analysis of protein structure networks (PSNs), especially via network centrality measurements and cluster coefficients, has led to identifying amino acid residues that play key functional roles and classifying amino acid residues in general. Whether these network properties examined in various studies are sensitive to subtle (yet biologically significant) conformational changes remained to be addressed. Here, we focused on four types of network centrality properties (betweenness, closeness, degree, and eigenvector centralities) for conformational changes upon ligand binding of a sensor protein (constitutive androstane receptor) and an allosteric enzyme (ribonucleotide reductase). We found that eigenvector centrality is sensitive and can distinguish salient structural features between protein conformational states while other centrality measures, especially closeness centrality, are less sensitive and rather generic with respect to the structural specificity. We also demonstrated that an ensemble-informed, modified PSN with static edges removed (which we term PSN*) has enhanced sensitivity at discerning structural changes. |
| Databáze: | OpenAIRE |
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