首页 | 本学科首页   官方微博 | 高级检索  
     


Comprehensive comparison of ligand-based virtual screening tools against the DUD data set reveals limitations of current 3D methods
Authors:Venkatraman Vishwesh  Pérez-Nueno Violeta I  Mavridis Lazaros  Ritchie David W
Affiliation:INRIA Nancy Grand Est, LORIA, 54506, Vandoeuvre-le?s-Nancy, France. vishwesh.venkatraman@loria.fr
Abstract:In recent years, many virtual screening (VS) tools have been developed that employ different molecular representations and have different speed and accuracy characteristics. In this paper, we compare ten popular ligand-based VS tools using the publicly available Directory of Useful Decoys (DUD) data set comprising over 100?000 compounds distributed across 40 protein targets. The DUD was developed initially to evaluate docking algorithms, but our results from an operational correlation analysis show that it is also well suited for comparing ligand-based VS tools. Although it is conventional wisdom that 3D molecular shape is an important determinant of biological activity, our results based on permutational significance tests of several commonly used VS metrics show that the 2D fingerprint-based methods generally give better VS performance than the 3D shape-based approaches for surprisingly many of the DUD targets. To help understand this finding, we have analyzed the nature of the scoring functions used and the composition of the DUD data set itself. We propose that to improve the VS performance of current 3D methods, it will be necessary to devise screening queries that can represent multiple possible conformations and which can exploit knowledge of known actives that span multiple scaffold families.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号