title: A hybrid approach for addressing ring flexibility in 3D database searching.
abstract: A hybrid approach for flexible 3D database searching is presented that addresses the problem of ring flexibility. It combines the explicit storage of up to 25 multiple conformations of rings, with up to eight atoms, generated by the 3D structure generator CORINA with the power of a torsional fitting technique implemented in the 3D database system UNITY. A comparison with the original UNITY approach, using a database with about 130,000 entries and five different pharmacophore queries, was performed. The hybrid approach scored, on an average, 10-20% more hits than the reference run. Moreover, specific problems with unrealistic hit geometries produced by the original approach can be excluded. In addition, the influence of the maximum number of ring conformations per molecule was investigated. An optimal number of 10 conformations per molecule is recommended.
authors.affiliation: Bayer AG, PH-R Structural Research, Wuppertal, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sadowski
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000737:chemistry; D016208:Databases, Factual; D018491:Dopamine Agonists / Q000737:chemistry; D015195:Drug Design; D017442:Histamine Agonists / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D011493:Protein Kinase C / Q000378:metabolism; D012984:Software
chemical_list: D000889:Anti-Arrhythmia Agents; D018491:Dopamine Agonists; D017442:Histamine Agonists; D011493:Protein Kinase C