Fingerprint design and engineering strategies: rationalizing and improving similarity search performance

Abstract

Fingerprints (FPs) are bit or integer string representations of molecular structure and properties, and are popular descriptors for chemical similarity searching. A major goal of similarity searching is the identification of novel active compounds on the basis of known reference molecules. In this review recent FP design and engineering strategies are discussed. New types of FPs continue to be replaced, often applying different design principles. FP engineering techniques have recently been introduced to further improve search performance and computational efficiency and elucidate mechanisms by which FPs recognize active compounds. In addition, through feature selection and hybridization techniques, standard FPs have been transformed into compound class-specific versions with further increased search performance. Moreover, scaffold hopping mechanisms have been explored. FPs will continue to play an important role in the search for novel active compounds.