Blind docking of pharmaceutically relevant compounds using RosettaLigand
Blind docking of pharmaceutically relevant compounds using RosettaLigand
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DOI：
10.1002/pro.192
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发表时间：
2009-09-01
期刊：
影响因子：
8
通讯作者：
Baker, David
中科院分区：
文献类型：
--
作者：
Davis, Ian W.;Raha, Kaushik;Baker, David
很难使用来自公共领域的数据正确验证将小分子配体对接到其蛋白质受体中的算法：预测不是盲目的，因为正确的结合模式已经知道，并且公共测试案例可能不代表感兴趣的化合物，例如药物先导。在这里，我们使用私人数据从一个真实的药物发现程序进行盲评估的RosettaLigand对接方法，并发现其性能是平均可比的最好的市售的当前小分子对接程序。RosettaLigand的优势在于使用Rosetta采样方法同时优化蛋白质侧链、蛋白质骨架和配体自由度;本文描述的广泛基准测试确定了该方案其他方面的缺点，并提出了改进该方法的明确途径。
It is difficult to properly validate algorithms that dock a small molecule ligand into its protein receptor using data from the public domain: the predictions are not blind because the correct binding mode is already known, and public test cases may not be representative of compounds of interest such as drug leads. Here, we use private data from a real drug discovery program to carry out a blind evaluation of the RosettaLigand docking methodology and find that its performance is on average comparable with that of the best commercially available current small molecule docking programs. The strength of RosettaLigand is the use of the Rosetta sampling methodology to simultaneously optimize protein sidechain, protein backbone and ligand degrees of freedom; the extensive benchmark test described here identifies shortcomings in other aspects of the protocol and suggests clear routes to improving the method.