Recovering the true targets of specific ligands by virtual screening of the protein data bank

• DOI: 10.1002/prot.10625
• Publication Date: 2004-02-26T20:39:43Z
• Authors: Nicodéme Paul; Esther Kellenberger; Guillaume Bret; Pascal Müller; Didier Rognan
• Keywords: Protein Data Bank; Docking (animal)

Abstract The Protein Data Bank (PDB) has been processed to extract a screening protein library (sc‐PDB) of 2148 entries. A knowledge‐based detection algorithm applied 18,000 PDB files find regular expressions corresponding either protein, ions, co‐factors, solvent, or ligand atoms. sc‐PDB database comprises high‐resolution X‐ray structures proteins for which (i) well‐defined active site exists, (ii) the bound‐ligand is small molecular weight molecule. screened by an inverse docking tool derived from GOLD program recover known target four unrelated ligands. Both and procedures are accurate enough rank true investigated ligands among top 1% scorers, with 70–100 fold enrichment respect random screening. Applying proposed procedure small‐sized generic was much less suggesting that shall be reserved rather selective compounds. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.