title: Local neighborhood behavior in a combinatorial library context.
abstract: This article revisits a particular aspect of the molecular similarity principle-the Neighborhood Behavior (NB) concept. Earlier, the NB optimality criterion was introduced to select descriptor spaces, combining a given descriptor set and a similarity metric, which optimally comply with the similarity principle. Here, we focus on a "local" analysis based on the neighborhood of individual bioactive compounds. The defined NB-score measures similarity-based virtual screening success when using individual actives as queries. Systematic studies of local NB have been performed on a large combinatorial library of compounds with reported IC (50) values for five proteases, involving more than 140 descriptor/metric combinations of various fragment- and pharmacophore-based descriptors and different similarity metrics. Although, for each descriptor/metrics combination, the NB-score heavily depends on the query compound, on the average, 2D pharmacophore-based descriptors outperformed their 3D counterparts.
authors.affiliation: Laboratoire d'InfoChime, UMR 7177 Université de Strasbourg-CNRS, Institut de Chimie, 4, rue Blaise Pascal, 67000 Strasbourg, France. horvath@chimie.u-strasbg.fr
authors.forename: Dragos
authors.initials: D
authors.lastname: Horvath
authors.forename: Christian
authors.initials: C
authors.lastname: Koch
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Gilles
authors.initials: G
authors.lastname: Marcou
authors.forename: Alexandre
authors.initials: A
authors.lastname: Varnek
mesh_terms: D016208:Databases, Factual; D015195:Drug Design; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D010447:Peptide Hydrolases