Mini-fingerprints detect similar activity of receptor ligands previously recognized only by three-dimensional pharmacophore-based methods

Mini-fingerprints (MFPs) are short binary bit string representations of mol ecular structure and properties, composed of few selected two-dimensional ( 2D) descriptors and a number of structural keys. MFPs were specifically des igned to recognize compounds with similar activity. Here we report that MFP s an capable of detecting similar activities of some druglike molecules, in cluding endothelin A antagonists and cll-adrenergic receptor ligands, the r ecognition of which was previously thought to depend on the use of multiple point three-dimensional (3D) pharmacophore methods. Thus, in these cases, MFPs and pharmacophore fingerprints produce similar results, although they define, in terms of their complexity, opposite ends of the spectrum of meth ods currently used to study molecular similarity or diversity. For each of the studied compound classes, comparison of MFP bit settings identified a c onsensus or signature pattern. Scaling factors can be applied to these bits in order to increase the probability of finding compounds with similar act ivity by virtual screening.