Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection - What can we learn from earlier mistakes?
Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection - What can we learn from earlier mistakes?
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DOI：
10.1007/s10822-007-9163-6
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Langer, Thierry
中科院分区：
文献类型：
--
作者：
Kirchmair, Johannes;Markt, Patrick;Langer, Thierry
在过去的几年中，已经发表了大量的评价性研究，调查3D虚拟筛选方法的性能。因此，特别是蛋白质-配体对接的评估在科学界面临着显着的兴趣。然而，比较虚拟筛选方法是一项重要的任务。一些出版物，特别是在分子对接领域，遭受的缺点，可能会影响结果的意义相当大。这些质量问题通常源于不良的研究设计、偏倚、使用不当或缺乏表达的富集描述符以及数据输出解释错误。在这篇综述中，我们分析了最近的文献评估三维虚拟筛选方法，重点是分子对接。我们强调有问题的问题，并提供如何提高计算研究的质量的指导方针。由于3D虚拟筛选协议一般通过其区分活性和非活性化合物的能力进行评估，我们总结了测试集的组成和制备对评估结果的影响。此外，我们研究了经典的富集参数和先进的描述符的三维虚拟筛选方法的性能的意义。此外，我们审查的意义和适用性的RMSD作为蛋白质配体对接算法和构象空间子采样算法的准确性的措施。
Within the last few years a considerable amount of evaluative studies has been published that investigate the performance of 3D virtual screening approaches. Thereby, in particular assessments of protein-ligand docking are facing remarkable interest in the scientific community. However, comparing virtual screening approaches is a non-trivial task. Several publications, especially in the field of molecular docking, suffer from shortcomings that are likely to affect the significance of the results considerably. These quality issues often arise from poor study design, biasing, by using improper or inexpressive enrichment descriptors, and from errors in interpretation of the data output. In this review we analyze recent literature evaluating 3D virtual screening methods, with focus on molecular docking. We highlight problematic issues and provide guidelines on how to improve the quality of computational studies. Since 3D virtual screening protocols are in general assessed by their ability to discriminate between active and inactive compounds, we summarize the impact of the composition and preparation of test sets on the outcome of evaluations. Moreover, we investigate the significance of both classic enrichment parameters and advanced descriptors for the performance of 3D virtual screening methods. Furthermore, we review the significance and suitability of RMSD as a measure for the accuracy of protein-ligand docking algorithms and of conformational space sub sampling algorithms.