Multifingerprint based similarity searches for targeted class compound selection

Molecular fingerprints are widely used for similarity-based virtual screening in drug discovery projects. In this paper we discuss the performance and the complementarity of nine two-dimensional fingerprints (Daylight, Unity, AlFi, Hologram, CATS, TRUST, Molprint 2D, ChemGPS, and ALOGP) in retrieving active molecules by similarity searching against a set of query compounds. For this purpose, we used biological data from HTS screening campaigns of four protein families (GPCRs, kinases, ion channels, and proteases). We have established threshold values for the similarity index (Tanimoto index) to be used as starting points for similarity searches. Based on the complementarities between the selections made by using different fingerprints we propose a multifingerprint approach as an efficient tool to balance the strengths and weaknesses of various fingerprints.