title: Database searching for compounds with similar biological activity using short binary bit string representations of molecules.
abstract: In an effort to identify biologically active molecules in compound databases, we have investigated similarity searching using short binary bit strings with a maximum of 54 bit positions. These "minifingerprints" (MFPs) were designed to account for the presence or absence of structural fragments and/or aromatic character, flexibility, and hydrogen-bonding capacity of molecules. MFP design was based on an analysis of distributions of molecular descriptors and structural fragments in two large compound collections. The performance of different MFPs and a reference fingerprint was tested by systematic "one-against-all" similarity searches of molecules in a database containing 364 compounds with different biological activities. For each fingerprint, the most effective similarity cutoff value was determined. An MFP accounting for only 32 structural fragments showed less than 2% false positive similarity matches and correctly assigned on average approximately 40% of the compounds with the same biological activity to a query molecule. Inclusion of three numerical two-dimensional (2D) molecular descriptors increased the performance by 15%. This MFP performed better than a complex 2D fingerprint. At a similarity cutoff value of 0.85, the 2D fingerprint totally eliminated false positives but recognized less than 10% of the compounds within the same activity class.
authors.affiliation: New Chemical Entities, Inc., Bothell, Washington 98011, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.forename: J W
authors.initials: JW
authors.lastname: Godden
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016208:Databases, Factual; D015195:Drug Design; D008024:Ligands; D011963:Receptors, GABA-A / Q000378:metabolism; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D016861:Cyclooxygenase Inhibitors; D008024:Ligands; D011963:Receptors, GABA-A