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Recovering the true targets of specific ligands by virtual screening of the protein data bank
Author(s) -
Paul Nicodéme,
Kellenberger Esther,
Bret Guillaume,
Müller Pascal,
Rognan Didier
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10625
Subject(s) - protein data bank (rcsb pdb) , protein data bank , virtual screening , chemistry , ligand (biochemistry) , docking (animal) , database , protein structure , computer science , stereochemistry , drug discovery , biochemistry , medicine , receptor , nursing
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. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.