Performance Evaluation of 2D Fingerprint and 3D Shape Similarity Methods in Virtual Screening
Performance Evaluation of 2D Fingerprint and 3D Shape Similarity Methods in Virtual Screening
复制标题
虚拟筛选中 2D 指纹和 3D 形状相似方法的性能评估
DOI：
10.1021/ci300030u
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发表时间：
2012-05-01
影响因子：
5.6
通讯作者：
Tang, Yun
中科院分区：
文献类型：
--
作者：
Hu, Guoping;Kuang, Guanglin;Tang, Yun
虚拟筛选（VS）可以通过基于配体或基于结构的方法来完成。近年来，越来越多的 2D 指纹和 3D 形状相似性方法被用于基于配体的 VS 中。为了评估这些基于配体的方法的性能，对有用诱饵 (DUD) 的定制目录进行了回顾性 VS。比较了 14 种 2D 指纹和四种 3D 形状相似方法的 VS 性能。结果表明，2D 指纹 ECFP_2 和 FCFP_4 比 3D 相形方法具有更好的性能。这些基于配体的方法还与基于结构的方法进行了比较，例如 Glide 对接和 Prime 分子力学广义 Born 表面积重新评分，这表明 2D 指纹和 3D 形状相似性方法可以在活性化合物的早期检索过程中产生更高的富集度。结果证明，基于配体的方法在速度和命中富集方面均优于基于对接的筛选。因此，在任何 VS 工作流程中首先考虑基于配体的方法将是一个明智的选择。
Virtual screening (VS) can be accomplished in either ligand- or structure-based methods. In recent times, an increasing number of 2D fingerprint and 3D shape similarity methods have been used in ligand-based VS. To evaluate the performance of these ligand-based methods, retrospective VS was performed on a tailored directory of useful decoys (DUD). The VS performances of 14 2D fingerprints and four 3D shape similarity methods were compared. The results revealed that 2D fingerprints ECFP_2 and FCFP_4 yielded better performance than the 3D Phase Shape methods. These ligand-based methods were also compared with structure-based methods, such as Glide docking and Prime molecular mechanics generalized Born surface area rescoring, which demonstrated that both 2D fingerprint and 3D shape similarity methods could yield higher enrichment during early retrieval of active compounds. The results demonstrated the superiority of ligand-based methods over the docking-based screening in terms of both speed and hit enrichment. Therefore, considering ligand-based methods first in any VS workflow would be a wise option.