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 molecular structure and properties, composed of few selected two-dimensional (2D) descriptors and a number of structural keys. MFPs were specifically designed to recognize compounds with similar activity. Here we report that MFPs are capable of detecting similar activities of some druglike molecules, including endothelin A antagonists and alpha(1)-adrenergic receptor ligands, the recognition 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 methods currently used to study molecular similarity or diversity. For each of the studied compound classes, comparison of MFP bit settings identified a consensus or signature pattern. Scaling factors can be applied to these bits in order to increase the probability of finding compounds with similar activity by virtual screening.
Xue
L
L
New Chemical Entities, Inc., 18804 North Creek Parkway, Suite 100, Bothell, Washington 98011, USA.
Stahura
F L
FL
Godden
J W
JW
Bajorath
J
J
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D016232:Endothelins / Q000037:antagonists & inhibitors; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry
D016232:Endothelins; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018340:Receptors, Adrenergic, alpha-1; D011956:Receptors, Cell Surface; D015842:Serine Proteinase Inhibitors; D000804:Angiotensin II