title: Coverage and bias in chemical library design.
abstract: The design of chemical libraries directed to target classes is an activity that requires the availability of ligand pharmacological data and/or protein structural data. On the basis of the knowledge derived from these data, chemical libraries directed mainly to G protein-coupled receptors, kinases, proteases, and nuclear receptors have been assembled. However, current design strategies widely overlook assessing the potential ability of the compounds contained in a focused library to provide uniform ample coverage of the protein family they intend to target. Here, we discuss the use of in silico target profiling methods as a means to estimate the actual scope of chemical libraries to probe entire protein families and illustrate its applicability in optimizing the composition of compound sets to achieve maximum coverage of the family with minimum bias to particular targets.
authors.affiliation: Chemotargets SL and Chemogenomics Laboratory, GRIB, Institut Municipal d'Investigació Mèdica and Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gregori-Puigjané
authors.forename: Jordi
authors.initials: J
authors.lastname: Mestres
mesh_terms: D019295:Computational Biology; D015195:Drug Design; D006801:Humans; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries