title: Composing compound libraries for hit discovery--rationality-driven preselection or random choice by structural diversity?
abstract: OBJECTIVE
  In order to identify new scaffolds for drug discovery, surface plasmon resonance is frequently used to screen structurally diverse libraries. Usually, hit rates are low and identification processes are time consuming. Hence, approaches which improve hit rates and, thus, reduce the library size are required.
  
  
  METHODS
  In this work, we studied three often used strategies for their applicability to identify inhibitors of PqsD. In two of them, target-specific aspects like inhibition of a homologous protein or predicted binding determined by virtual screening were used for compound preselection. Finally, a fragment library, covering a large chemical space, was screened and served as comparison.
  
  
  CONCLUSIONS
  Indeed, higher hit rates were observed for methods employing preselected libraries indicating that target-oriented compound selection provides a time-effective alternative.
authors.affiliation: Department Drug Design & Optimization, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Weidel
authors.forename: Matthias
authors.initials: M
authors.lastname: Negri
authors.forename: Martin
authors.initials: M
authors.lastname: Empting
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinsberger
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D054852:Small Molecule Libraries