title: Virtual fragment screening: an exploration of various docking and scoring protocols for fragments using Glide.
abstract: Fragment-based drug discovery approaches allow for a greater coverage of chemical space and generally produce high efficiency ligands. As such, virtual and experimental fragment screening are increasingly being coupled in an effort to identify new leads for specific therapeutic targets. Fragment docking is employed to create target-focussed subset of compounds for testing along side generic fragment libraries. The utility of the program Glide with various scoring schemes for fragment docking is discussed. Fragment docking results for two test cases, prostaglandin D2 synthase and DNA ligase, are presented and compared to experimental screening data. Self-docking, cross-docking, and enrichment studies are performed. For the enrichment runs, experimental data exists indicating that the docking decoys in fact do not inhibit the corresponding enzyme being examined. Results indicate that even for difficult test cases fragment docking can yield enrichments significantly better than random.
authors.affiliation: AstraZeneca, R&D Boston, 35 Gatehouse Dr., Waltham, MA, 02451, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Kawatkar
authors.forename: Hongming
authors.initials: H
authors.lastname: Wang
authors.forename: Ryszard
authors.initials: R
authors.lastname: Czerminski
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
mesh_terms: D001665:Binding Sites; D017076:Computer-Aided Design; D011088:DNA Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D055808:Drug Discovery; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008024:Ligands; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000627:therapeutic use; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D054834:Lipocalins; D054852:Small Molecule Libraries; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D011088:DNA Ligases