“Fuzzy” pharmacophores for virtual screening and library design

CINF 77

Gisbert Schneider, g.schneider@modlab.de, Institute of Organic Chemistry & Chemical Biology, Johann Wolfgang Goethe-University, Siesmayerstr. 70, D-60323 Frankfurt, Germany
The degree of scaffold diversity of virtual hits obtained by similarity searching is influenced by the molecular representation. Different hit lists are found at different level of abstraction from the atomic structure. A high degree of abstraction is thought to facilitate the identification of novel structures that exhibit a similar pharmacological profile as the query. We have developed molecular descriptors that allow for variable degrees of fuzziness of potential pharmacophore-points. The theoretical concept and several prospective applications will be presented. These include scaffold-hopping applications and the design of natural-product derived combinatorial libraries.