Surflex-Dock: Docking benchmarks and real-world application.
Surflex-Dock: Docking benchmarks and real-world application.
复制标题
DOI：
10.1007/s10822-011-9533-y
复制
发表时间：
2012-06
影响因子：
3.5
通讯作者：
Jain, Ajay N.
中科院分区：
文献类型：
--
作者：
Spitzer, Russell;Jain, Ajay N.
关键词：
分子对接的基准历来专注于重新对接确定的蛋白质-配体复合体的同源配体以测量几何姿势预测精度，而虚拟筛选性能的测量一直专注于越来越大和多样化的目标蛋白质结构、同源配体和各种类型的诱饵集。在这里，姿势预测是在ASTEX不同的85个蛋白质配体复合体集合上报告的，而虚拟筛选性能是在40个蛋白质目标的DUD集合上报告的。在这两种情况下，目标和配体的制备结构都是由研讨会组织者提供的。重新编制的数据集产生的结果与Surflex-Dock以前关于这两个基准的报告没有明显不同。复杂的预优化导致蛋白质坐标的微小变化对观察到的性能有很大影响，突显了同源配体重新对接用于姿势预测评估的局限性。为交叉对接开发的对接协议解决了蛋白质的灵活性并产生了预测姿势的离散家族，为姿势预测产生了显著更好的性能。虚拟筛选性能的表现表明，使用和组合多种筛选方法：对接、2D分子相似性和3D分子相似性是有益的。此外，使用多个蛋白质构象显著改善了筛选浓缩。
Benchmarks for molecular docking have historically focused on re-docking the cognate ligand of a well-determined protein-ligand complex to measure geometric pose prediction accuracy, and measurement of virtual screening performance has been focused on increasingly large and diverse sets of target protein structures, cognate ligands, and various types of decoy sets. Here, pose prediction is reported on the Astex Diverse set of 85 protein ligand complexes, and virtual screening performance is reported on the DUD set of 40 protein targets. In both cases, prepared structures of targets and ligands were provided by symposium organizers. The re-prepared data sets yielded results not significantly different than previous reports of Surflex-Dock on the two benchmarks. Minor changes to protein coordinates resulting from complex pre-optimization had large effects on observed performance, highlighting the limitations of cognate ligand re-docking for pose prediction assessment. Docking protocols developed for cross-docking, which address protein flexibility and produce discrete families of predicted poses, produced substantially better performance for pose prediction. Performance on virtual screening performance was shown to benefit by employing and combining multiple screening methods: docking, 2D molecular similarity, and 3D molecular similarity. In addition, use of multiple protein conformations significantly improved screening enrichment.
登录
查看更多内容
影响因子：
5.6
作者：
JONES, G;WILLETT, P;GLEN, RC
通讯作者：
GLEN, RC
影响因子：
7.3
作者：
Hawkins, Paul C. D.;Skillman, A. Geoffrey;Nicholls, Anthony
通讯作者：
Nicholls, Anthony
影响因子：
3.5
作者：
Jain, Ajay N.
通讯作者：
Jain, Ajay N.
影响因子：
3.5
作者：
Rarey, M;Kramer, B;Lengauer, T
通讯作者：
Lengauer, T
影响因子：
7.3
作者：
Cleves, Ann E.;Jain, Ajay N.
通讯作者：
Jain, Ajay N.