Structure of protein interaction networks and their implications on drug design.
Structure of protein interaction networks and their implications on drug design.
复制标题
蛋白质相互作用网络的结构及其对药物设计的影响。
DOI：
10.1371/journal.pcbi.1000550
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发表时间：
2009-10
影响因子：
4.3
通讯作者：
Kitano H
中科院分区：
文献类型：
--
作者：
Hase T;Tanaka H;Suzuki Y;Nakagawa S;Kitano H
蛋白质-蛋白质相互作用网络（PIN）是丰富的信息来源，使生物系统的网络特性被理解。对芽殖酵母和人类PIN的拓扑和统计特性的研究表明，它们具有丰富的规模，并被配置为高度优化的容差（HOT）网络，类似于互联网的路由器级拓扑。这与声称这种网络是无标度的，并通过简单的偏好连接过程配置不同。进一步的分析表明，形成网络骨干的中间度节点之间存在广泛的互连。必需基因、合成致死基因、合成致病基因和人类药物靶基因的度分布表明，具有中到低度节点的节点之间存在有利的药物靶点。这种网络性质为靶向不太突出的节点的组合药物提供了基本原理，以增加协同功效并产生更少的副作用。关于蛋白质之间相互作用的全基因组数据现已可用，蛋白质相互作用网络是理解疾病和找到准确药物靶点的关键。这项研究揭示了蛋白质相互作用网络（PIN）的骨架的结构特性类似于互联网路由器级拓扑结构，通过使用全基因组的芽殖酵母和人类PIN的统计分析。这种类型的网络被称为高度优化的容差（HOT）网络，它对组件中的故障具有鲁棒性，并确保高水平的通信。此外，我们还发现，大量最成功的药物靶蛋白都在人PIN的主链上。我们列出了人类PIN骨架上的蛋白质，这可能有助于制药公司更有效地寻找新的药物靶点。
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. Genome-wide data on interactions between proteins are now available, and networks of protein interactions are the keys to understanding diseases and finding accurate drug targets. This study revealed that the architectural properties of the backbones of protein interaction networks (PINs) were similar to those of the Internet router-level topology by using statistical analyses of genome-wide budding yeast and human PINs. This type of network is known as a highly optimized tolerance (HOT) network that is robust against failures in its components and that ensures high levels of communication. Moreover, we also found that a large number of the most successful drug-target proteins are on the backbone of the human PIN. We made a list of proteins on the backbone of the human PIN, which may help drug companies to search more efficiently for new drug targets.
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影响因子：
14.9
作者：
Güldener U;Münsterkötter M;Oesterheld M;Pagel P;Ruepp A;Mewes HW;Stümpflen V
通讯作者：
Stümpflen V
影响因子：
9.8
作者：
Batada NN;Reguly T;Breitkreutz A;Boucher L;Breitkreutz BJ;Hurst LD;Tyers M
通讯作者：
Tyers M
影响因子：
5.8
作者：
Rzhetsky, A;Gomez, SM
通讯作者：
Gomez, SM
DOI：
10.1073/pnas.0701722105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Feldman, Igor;Rzhetsky, Andrey;Vitkup, Dennis
通讯作者：
Vitkup, Dennis
影响因子：
4
作者：
Albert, R
通讯作者：
Albert, R