title: Enrichment of virtual hits by progressive shape-matching and docking.
abstract: The main applications of virtual chemical screening include the selection of a minimal receptor-relevant subset of a chemical library with a maximal chemical diversity. We have previously reported that the combination of ligand-centric and receptor-centric virtual screening methods may provide a compromise between computational time and accuracy during the hit enrichment process. In the present work, we propose a "progressive distributed docking" method that improves the virtual screening process using an iterative combination of shape-matching and docking steps. Known ligands with low docking scores were used as initial 3D templates for the shape comparisons with the chemical library. Next, new compounds with good template shape matches and low receptor docking scores were selected for the next round of shape searching and docking. The present iterative virtual screening process was tested for enriching peroxisome proliferator-activated receptor and phosphoinositide 3-kinase relevant compounds from a selected subset of the chemical libraries. It was demonstrated that the iterative combination improved the lead-hopping practice by improving the chemical diversity in the selected list of virtual hits.
authors.affiliation: Department of Biological Sciences, Research Center for Women's Diseases, Sookmyung Women's University, Hyochangwongil 52, Yongsan-gu, Seoul 140-742, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Choi
authors.forename: Ningning
authors.initials: N
authors.lastname: He
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Sukjoon
authors.initials: S
authors.lastname: Yoon
mesh_terms: D001665:Binding Sites; D030562:Databases, Protein; D057166:High-Throughput Screening Assays; D008024:Ligands; D008958:Models, Molecular; D047492:Peroxisome Proliferator-Activated Receptors / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry*; D025341:Principal Component Analysis; D011487:Protein Conformation; D054852:Small Molecule Libraries
chemical_list: D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D054852:Small Molecule Libraries; D019869:Phosphatidylinositol 3-Kinases