CombiDOCK: Structure-based combinatorial docking and library design

被引：64

作者：

Sun, Y ^{[1
]}

Ewing, TJA ^{[1
]}

Skillman, AG ^{[1
]}

Kuntz, ID ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 1998年 / 12卷 / 06期

关键词：

combinatorial library design; molecular docking; structure-based drug design;

D O I：

10.1023/A:1008036704754

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have developed a strategy for efficiently docking a large combinatorial library into a target receptor. For each scaffold orientation, all potential fragments are attached to the scaffold, their interactions with the receptor are individually scored and factorial combinations of fragments are constructed. To test its effectiveness, this approach is compared to two simple control algorithms. Our method is more efficient than the controls at selecting best scoring molecules and at selecting fragments for the construction of an exhaustive combinatorial library. We also carried out a retrospective analysis of the experimental results of a 10 x 10 x 10 exhaustive combinatorial library. An enrichment factor of approximately 4 was found for identifying the compounds in the library that are active at 330 nM.

引用

页码：597 / 604

页数：8

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