Library screening by fragment-based docking
Library screening by fragment-based docking
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DOI：
10.1002/jmr.981
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发表时间：
2010-03-01
影响因子：
2.7
通讯作者：
Caflisch, Amedeo
中科院分区：
文献类型：
--
作者：
Huang, Danzhi;Caflisch, Amedeo
我们回顾了通过基于片段的大量小分子对接进行高通量筛选的计算工具。介绍了六种不同酶、四种蛋白酶和两种蛋白激酶的应用。值得注意的是，在每次高通量对接活动中都发现了几种低微摩尔抑制剂。缺乏亚微摩尔抑制剂的可能原因是可用化合物库所覆盖的化学空间的一小部分，以及用于评分的方法的近似值以及目标蛋白的刚性构象的使用。版权所有 (C) 2009 John Wiley & Sons, Ltd.
We review our computational tools for high-throughput screening by fragment-based docking of large collections of small molecules. Applications to six different enzymes, four proteases, and two protein kinases, are presented. Remarkably, several low-micromolar inhibitors were discovered in each of the high-throughput docking campaigns. Probable reasons for the lack of submicromolar inhibitors are the tiny fraction of chemical space covered by the libraries of available compounds, as well as the approximations in the methods employed for scoring, and the use of a rigid conformation of the target protein. Copyright (C) 2009 John Wiley & Sons, Ltd.