title: Design of chemical space networks using a Tanimoto similarity variant based upon maximum common substructures.
abstract: Chemical space networks (CSNs) have recently been introduced as an alternative to other coordinate-free and coordinate-based chemical space representations. In CSNs, nodes represent compounds and edges pairwise similarity relationships. In addition, nodes are annotated with compound property information such as biological activity. CSNs have been applied to view biologically relevant chemical space in comparison to random chemical space samples and found to display well-resolved topologies at low edge density levels. The way in which molecular similarity relationships are assessed is an important determinant of CSN topology. Previous CSN versions were based on numerical similarity functions or the assessment of substructure-based similarity. Herein, we report a new CSN design that is based upon combined numerical and substructure similarity evaluation. This has been facilitated by calculating numerical similarity values on the basis of maximum common substructures (MCSs) of compounds, leading to the introduction of MCS-based CSNs (MCS-CSNs). This CSN design combines advantages of continuous numerical similarity functions with a robust and chemically intuitive substructure-based assessment. Compared to earlier version of CSNs, MCS-CSNs are characterized by a further improved organization of local compound communities as exemplified by the delineation of drug-like subspaces in regions of biologically relevant chemical space.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, 53113, Bonn, Germany.
authors.forename: Bijun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, 53113, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Vogt
authors.affiliation: BIO5 Institute, University of Arizona, 1657 East Helen Street, Tucson, AZ, 85721, USA.|Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ, 85004, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Maggiora
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, 53113, Bonn, Germany. bajorath@bit.uni-bonn.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D016000:Cluster Analysis; D062126:Databases, Chemical; D019277:Entropy; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D017481:Receptors, Somatostatin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5
keywords: Biologically relevant chemical space; Chemical space networks; Drug-like subspaces; Maximum common substructures; Network science; Tanimoto similarity