title: Directed R-group combination graph: a methodology to uncover structure-activity relationship patterns in a series of analogues.
abstract: A graphical method is introduced to study details of structure-activity relationships (SARs) in analogue series that further extends conventional analysis of analogues using R-group tables or related approaches and that provides additional and more differentiated SAR information. The newly designed graph structure represents entire series of analogues in a consistent manner, regardless of their size and complexity of substitution patterns. The approach is specifically tailored toward a systematic exploration and intuitive interpretation of SAR features involving different R-groups and their combinations. Analogues and their potency information are systematically organized on the basis of R-group combinations that are present in a series. This organization scheme results in graph components that represent well-defined SAR patterns. Analysis of these patterns provides an immediate access to critical substitution sites and R-group combinations, favorable and unfavorable R-groups, or nonadditive potency effects of multisite substitutions. Furthermore, the data structure makes it possible to design new analogues by combining favorable R-group combinations derived from different compounds.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstrasse 2, D-53113 Bonn, Germany.
authors.forename: Anne Mai
authors.initials: AM
authors.lastname: Wassermann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D003196:Computer Graphics; D015195:Drug Design; D005663:Furans / Q000737:chemistry; D008958:Models, Molecular; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors
chemical_list: D005663:Furans; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D010880:Piperidines; D044105:Receptor, Melanocortin, Type 4; D017447:Receptors, Dopamine D1