Cheeseright Timothy J, Mackey Mark D, Melville James L, Vinter Jeremy G
Cresset BioMolecular Discovery Ltd., BioPark Hertfordshire, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, United Kingdom.
J Chem Inf Model. 2008 Nov;48(11):2108-17. doi: 10.1021/ci800110p.
FieldScreen, a ligand-based Virtual Screening (VS) method, is described. Its use of 3D molecular fields makes it particularly suitable for scaffold hopping, and we have rigorously validated it for this purpose using a clustered version of the Directory of Useful Decoys (DUD). Using thirteen pharmaceutically relevant targets, we demonstrate that FieldScreen produces superior early chemotype enrichments, compared to DOCK. Additionally, hits retrieved by FieldScreen are consistently lower in molecular weight than those retrieved by docking. Where no X-ray protein structures are available, FieldScreen searches are more robust than docking into homology models or apo structures.
本文描述了一种基于配体的虚拟筛选（VS）方法——FieldScreen。它对三维分子场的使用使其特别适用于骨架跃迁，并且我们已使用有用诱饵目录（DUD）的聚类版本对此进行了严格验证。通过13个与药学相关的靶点，我们证明，与DOCK相比，FieldScreen能产生更优异的早期化学型富集。此外，FieldScreen检索到的命中物的分子量始终低于对接检索到的命中物。在没有X射线蛋白质结构可用的情况下，FieldScreen搜索比对接同源模型或无配体结构更稳健。
