title: Exploring SAR continuity in the vicinity of activity cliffs.
abstract: Activity cliffs are formed by structurally similar compounds with significant differences in potency and represent an extreme form of structure-activity relationships discontinuity. By contrast, regions of structure-activity relationships continuity in compound data sets result from the presence of structurally increasingly diverse compounds retaining similar activity. Previous studies have revealed that structure-activity relationships information extracted from large compound data sets is often heterogeneous in nature containing both continuous and discontinuous structure-activity relationships components. Structure-activity relationships discontinuity and continuity are often represented by different compound series, independent of each other. Here, we have searched different compound data sets for the presence of structure-activity relationships continuity within the vicinity of prominent activity cliffs. For this purpose, we have designed and implemented a computational approach utilizing particle swarm optimization to examine the structural neighborhood of activity cliffs for continuous structure-activity relationships components. Structure-activity relationships continuity in the structural neighborhood of activity cliffs was relatively rarely observed. However, in a number of cases, notable structure-activity relationships continuity was detected in the vicinity of prominent activity cliffs. Exemplary local structure-activity relationships environments displaying these characteristics were analyzed in detail. Thus, the structure-activity relationships environment of activity cliffs must not necessarily be discontinuous in nature, and local structure-activity relationships continuity and discontinuity can occur in a concerted manner in series of structurally related compounds.
authors: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstrasse 2, Germany.
authors: Vigneshwaran
authors: V
authors: Namasivayam
authors: Preeti
authors: P
authors: Iyer
authors: Jürgen
authors: J
authors: Bajorath
mesh_terms: D000465:Algorithms; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes