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Relating Three-Dimensional Structures to Protein Networks Provides Evolutionary Insights
Philip M. Kim,1Long J. Lu,1Yu Xia,4,5Mark B. Gerstein1,2,3*
Most studies of protein networks operate on a high level ofabstraction, neglecting structural and chemical aspects of eachinteraction. Here, we characterize interactions by using atomic-resolutioninformation from three-dimensional protein structures. We findthat some previously recognized relationships between networktopology and genomic features (e.g., hubs tending to be essentialproteins) are actually more reflective of a structural quantity,the number of distinct binding interfaces. Subdividing hubswith respect to this quantity provides insight into their evolutionaryrate and indicates that additional mechanisms of network growthare active in evolution (beyond effective preferential attachmentthrough gene duplication).
1 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. 2 Department of Computer Science, Yale University, New Haven, CT 06520, USA. 3 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA. 4 Bioinformatics Program, Boston University, Boston, MA 02215, USA. 5 Department of Chemistry, Boston University, Boston, MA 02215, USA.
* To whom correspondence should be addressed. E-mail: mark.gerstein{at}yale.edu
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