Recovering the true targets of specific ligands by virtual screening of the Protein Data Bank

被引:86
作者
Paul, N [1 ]
Kellenberger, E [1 ]
Bret, G [1 ]
Müller, P [1 ]
Rognan, D [1 ]
机构
[1] CNRS UMR 7081, Bioinformat Grp, Lab Pharmacochim & Commun Cellulaire, F-67401 Illkirch Graffenstaden, France
关键词
docking; PDB; protein library; virtual screening;
D O I
10.1002/prot.10625
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
The Protein Data Bank (PDB) has been processed to extract a screening protein library (sc-PDB) of 2148 entries. A knowledge-based detection algorithm has been applied to 18,000 PDB files to find regular expressions corresponding to either protein, ions, co-factors, solvent, or ligand atoms. The sc-PDB database comprises high-resolution X-ray structures of proteins for which (i) a well-defined active site exists, (ii) the bound-ligand is a small molecular weight molecule. The database has been screened by an inverse docking tool derived from the GOLD program to recover the known target of four unrelated ligands. Both the database and the inverse screening procedures are accurate enough to rank the true target of the four investigated ligands among the top 1% scorers, with 70-100 fold enrichment with respect to random screening. Applying the proposed screening procedure to a small-sized generic ligand was much less accurate suggesting that inverse screening shall be reserved to rather selective compounds. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:671 / 680
页数:10
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