Measuring CAMD technique performance: A virtual screening case study in the design of validation experiments
Measuring CAMD technique performance: A virtual screening case study in the design of validation experiments
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DOI：
10.1007/s10822-004-4067-1
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Hindle, SA
中科院分区：
文献类型：
--
作者：
Good, AC;Hermsmeier, MA;Hindle, SA
计算化学的动态性质和相对年轻的时代使得新颖的算法继续快速发展。这些努力往往是以对所述技术进行广泛的实验验证为代价的，阻碍了对其潜在效用和局限性的更深入理解。在这里，我们通过设计更好地反映现实世界应用目标的验证实验来解决基于配体的虚拟筛选描述符的这个问题。应用新定义的化学型富集方法，各种二维和三维 (2D/3D) 相似性描述符已在四种不同目标类型的数据集中进行了广泛比较。所述数据集中的抑制剂包含表现出广泛的子结构功能、大小和灵活性的分子，允许在无数设置中进行描述符比较。检查这些条件下的相对描述符性能，包括使用更典型的虚拟筛选验证实验获得的结果。还在所获得的结果的背景下讨论了所述描述符的最佳应用指南，以及指纹过滤的潜在效用。
The dynamic nature and comparatively young age of computational chemistry is such that novel algorithms continue to be developed at a rapid pace. Such efforts are often wrought at the expense of extensive experimental validations of said techniques, preventing a deeper understanding of their potential utility and limitations. Here we address this issue for ligand-based virtual screening descriptors through design of validation experiments that better reflect the aims of real world application. Applying the newly defined chemotype enrichment approach, a variety of two- and three-dimensional (2D/3D) similarity descriptors have been compared extensively across data sets from four diverse target types. The inhibitors within said data sets contain molecules exhibiting a wide array of substructure functionality, size and flexibility, permitting descriptor comparison in myriad settings. Relative descriptor performance under these conditions is examined, including results obtained using more typical virtual screening validation experiments. Guidelines for optimal application of said descriptors are also discussed in the context of the results obtained, as is the potential utility of fingerprint filtering.