University of Konstanz
Graduiertenkolleg / PhD Program
Computer and Information Science

Colloquium of the Department and the PhD Program

title

Scaffold Hunter: Interactive Exploration of Chemical Space

speaker

Dr. Stefan Wetzel, Novartis
Basel, Switzerland

date & place

Wednesday, 07.07.2010, 16:15 h
Room C 252

abstract

Efficient navigation of chemical space and analyses of information-rich data sets that combine chemical structure with biochemical and biological data require powerful cheminformatics methods. The talk describes the development of the Scaffold Hunter a highly interactive tool that fosters intuitive recognition of complex structural relationships associated with bioactivity, allowing interactive navigation in chemical space. The Scaffold Hunter reads compound structure and bioactivity data, automatically generates the compound scaffolds, correlates them in a tree-like arrangement representing hierarchical relationships between the scaffolds in chemical space, and annotates them with the bioactivity data. Interactive brachiation along the branches of the tree from structurally complex to simple scaffolds with retained yet varying bioactivity can lead to the identification of new inhibitor types for a given target protein. We provide proof-of-concept by database analysis and experimental identification of novel inhibitor and activator scaffolds for pyruvate kinase. A second approach utilizes tree-merging to identify novel, biologically relevant scaffold structures and their putative targets. This application led to the identification of modulators of the STAT proteins, the sphingomyelinases and monoamine oxidase 1 and 2.