Structure-Based Virtual Screening of Commercially Available Compound Libraries.
Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).
Center for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus Box 7363, Marsico Hall, room 3205, 125 Mason Farm Road, Chapel Hill, NC, 27599-7363, USA. dmitri.kireev@unc.edu.
Dmitri
D
Kireev
D000818:Animals; D017076:Computer-Aided Design; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D046209:Electrophoresis, Microchip / Q000379:methods; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D012984:Software; D057188:Workflow
D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries
Commercially available compounds; Docking; Experimental testing; Procurement; Scoring function; Structure-based virtual screening; Triage