Small-World Phenomena in Chemical Library Networks: Application to Fragment-Based Drug Discovery
Small-World Phenomena in Chemical Library Networks: Application to Fragment-Based Drug Discovery
复制标题
化学图书馆网络中的小世界现象：在基于片段的药物发现中的应用
DOI：
10.1021/ci900123v
复制
发表时间：
2009
影响因子：
5.6
通讯作者：
M. Orita
中科院分区：
文献类型：
--
作者：
Naoki Tanaka;K. Ohno;T. Niimi;Ayako Moritomo;K. Mori;M. Orita
在各个领域中的各种各样的网络被描述为小世界网络。无标度网络是小世界网络的一个代表，在无标度网络中，节点的接触数（度分布）遵循幂律。虽然在化学信息学领域已经发现了几个幂律分布的例子，但尚未分析化学库的网络结构。在这里，我们发现，小世界现象不仅在现有的化学库中观察到，而且在虚拟库中产生的结构多样的片段时，表示为网络。在此观察的基础上，我们提出了一个有效的化合物优先级的方法片段为基础的药物发现（FBDD）将选择这些片段作为起点，使连接的化合物成为枢纽库中，因此允许识别许多类似的化合物时，所有对所有的片段连接进行。此外，我们的分析表明，各种接头的网络结构，从而对多样性的化合物合成的连接片段命中有显着的影响。
A wide variety of networks in various fields have been characterized as small-world networks. In scale-free networks, a representative class of small-world networks, numbers of contacts (degree distributions) of nodes follow power laws. Although several examples of power-law distributions have been found in the field of chemoinformatics, the network structures of chemical libraries have not been analyzed. Here, we show that small-world phenomena are observed not only in existing chemical libraries but also in virtual libraries generated from structurally diverse fragments when represented as networks. On the basis of this observation, we propose that an efficient compound-prioritization method of fragment-based drug discovery (FBDD) would be to select those fragments as a starting point such that the linked compounds become hubs in the library and therefore allow identification of many similar compounds when all-to-all fragment linkings are performed. Moreover, our analyses indicated that the variety of linkers had a marked influence on the network structure and thus on the diversity of the compounds synthesized by linking fragment hits.