University of Sheffield
Similarity searching using a single bioactive reference structure is a well-established technique for accessing chemical structure databases. This paper describes two extensions of the basic approach. First, we discuss the use of group fusion to combine the results of similarity searches when multiple reference structures are available. We demonstrate that this technique is notably more effective than conventional similarity searching, especially in scaffold-hopping searches for structurally diverse sets of active molecules. Second, we make the assumption that the nearest neighbours resulting from a similarity search, using a single bioactive reference structure, are also active and use this assumption to implement approximate forms of group fusion, substructural analysis and binary kernel discrimination. This approach, called turbo similarity searching, is notably more effective than conventional similarity searching.