结合FRED、DOCK和Surflex的基于结构的快速虚拟配体筛选。

Fast structure-based virtual ligand screening combining FRED, DOCK, and Surflex.

作者信息

Miteva Maria A, Lee Wen H, Montes Matthieu O, Villoutreix Bruno O

机构信息

INSERM U648, University Paris 5, Paris 75006, France.

出版信息

J Med Chem. 2005 Sep 22;48(19):6012-22. doi: 10.1021/jm050262h.

DOI:10.1021/jm050262h

PMID:16162004

Abstract

A protocol was devised in which FRED, DOCK, and Surflex were combined in a multistep virtual ligand screening (VLS) procedure to screen the pocket of four different proteins. One goal was to evaluate the impact of chaining "freely available packages to academic users" on docking/scoring accuracy and CPU time consumption. A bank of 65 660 compounds including 49 known actives was generated. Our procedure is successful because docking/scoring parameters are tuned according to the nature of the binding pocket and because a shape-based filtering tool is applied prior to flexible docking. The obtained enrichment factors are in line with those reported in recent studies. We suggest that consensus docking/scoring could be valuable to some drug discovery projects. The present protocol could process the entire bank for one receptor in less than a week on one processor, suggesting that VLS experiments could be performed even without large computer resources.

摘要

设计了一种方案，其中FRED、DOCK和Surflex在多步虚拟配体筛选（VLS）程序中结合，以筛选四种不同蛋白质的口袋。一个目标是评估“向学术用户免费提供软件包”对对接/评分准确性和CPU时间消耗的影响。生成了一组包含49种已知活性物质的65660种化合物。我们的方法是成功的，因为对接/评分参数根据结合口袋的性质进行了调整，并且因为在灵活对接之前应用了基于形状的过滤工具。获得的富集因子与最近研究中报道的一致。我们建议，共识对接/评分对一些药物发现项目可能有价值。本方案在一个处理器上不到一周就能处理一个受体的整个化合物库，这表明即使没有大型计算机资源也可以进行VLS实验。