title: Method for Systematic Assessment of Chemical Changes in Molecular Scaffolds with Conserved Topology and Application to the Analysis of Scaffold-Activity Relationships.
abstract: Sets of scaffolds with conserved molecular topology are abundant among drugs and bioactive compounds. Core structure topology is one of the determinants of biological activity. Heteroatom replacements and/or bond order variation render topologically equivalent scaffolds chemically distinct and also contribute to differences in the biological activity of compounds containing these scaffolds. Relationships between core structure topology, chemical modifications, and observed activity profiles are difficult to analyze. A computational method is introduced to consistently assess chemical transformations that distinguish scaffolds with conserved topology. The methodology is applied to quantify chemical differences in conserved topological environments and systematically relate chemical changes in topologically equivalent scaffolds to associated activity profiles.
authors.affiliation: Department of Life Science Informatics, Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113 Bonn (Germany) tel: +49-228-2699-306; fax: +49-228-2699-341.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Life Science Informatics, Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113 Bonn (Germany) tel: +49-228-2699-306; fax: +49-228-2699-341.
authors.forename: Bijun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Life Science Informatics, Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, 53113 Bonn (Germany) tel: +49-228-2699-306; fax: +49-228-2699-341. bajorath@bit.uni-bonn.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D003198:Computer Simulation; D062126:Databases, Chemical; D008958:Models, Molecular; D015394:Molecular Structure
keywords: Activity profiles.; Chemical transformations; Hierarchical structural relationships; Molecular topology; Scaffolds; Structure-activity relationships