Docking Screens for Novel Ligands Conferring New Biology.
Docking Screens for Novel Ligands Conferring New Biology.
复制标题
DOI：
10.1021/acs.jmedchem.5b02008
复制
发表时间：
2016-05-12
影响因子：
7.3
通讯作者：
Shoichet BK
中科院分区：
文献类型：
--
作者：
Irwin JJ;Shoichet BK
现在可以在几天或几周内将 1000 万个分子的文库与目标对接。当筛选的分子上市后，可以对其进行快速测试以寻找新的先导化合物。尽管对接保留了重要的缺点（它无法准确计算亲和力，甚至无法可靠地对高分分子进行排序），但它通常可以区分可能的配体和不太可能的配体，命中率通常高于 10%。在这里，我们总结了支持这些进步的库、目标质量和方法的改进，以及使对接变得容易的开放获取资源。概述了最近的新配体对接筛选，以及支持它们的结合、晶体学和体内测定。与任何技术一样，控制至关重要，并对关键的实验进行审查。通过这样的控制，对接活动可以找到具有新化学型的配体，通常会揭示新的生物学，这可能是对接在未来几年中最大的影响。
It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably rank order high-scoring molecules), it can often can distinguish likely from unlikely ligands, often with hit rates above 10%. Here we summarize the improvements in libraries, target quality, and methods that have supported these advances, and the open access resources that make docking accessible. Recent docking screens for new ligands are sketched, as are the binding, crystallographic, and in vivo assays that support them. Like any technique, controls are crucial, and key experimental ones are reviewed. With such controls, docking campaigns can find ligands with new chemotypes, often revealing the new biology that may be docking’s greatest impact over the next few years.
影响因子：
3.8
作者：
Ramirez UD;Nikonova AS;Liu H;Pecherskaya A;Lawrence SH;Serebriiskii IG;Zhou Y;Robinson MK;Einarson MB;Golemis EA;Jaffe EK
通讯作者：
Jaffe EK