Structure of protein interaction networks and their implications on drug design.

Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly opti...

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Autores principales: Takeshi Hase, Hiroshi Tanaka, Yasuhiro Suzuki, So Nakagawa, Hiroaki Kitano
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/c9cec5b8c64f4192a970311ef633ebfb
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Sumario:Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects.