title: Formal concept analysis for the identification of molecular fragment combinations specific for active and highly potent compounds.
abstract: We introduce fragment formal concept analysis (FragFCA) to study complex relationships between fragments in active compounds taking potency information into account. Fragment combinations that are unique to active or highly potent compounds or that are shared by molecules having different or overlapping activity profiles are systematically identified using chemically intuitive queries of varying complexity. The methodology is applied to analyze fragment distributions in antagonists of seven G protein coupled receptor targets and identify signature fragments. Pairs or triplets of molecular fragments are found to be most specific for different activity profiles and compound potency levels. In addition, we demonstrate the ability of FragFCA to identify selective hits in high-throughput screening data sets.
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: Eugen
authors.initials: E
authors.lastname: Lounkine
authors.forename: Jens
authors.initials: J
authors.lastname: Auer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D000465:Algorithms; D001679:Biogenic Amines; D002403:Cathepsins / Q000037:antagonists & inhibitors; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D008956:Models, Chemical; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D001679:Biogenic Amines; D043562:Receptors, G-Protein-Coupled; D002403:Cathepsins