Molecular complexity effects and fingerprint based similarity search strategies [Elektronische Ressource] / vorgelegt von Yuan Wang

Molecular Complexity Effectsand Fingerprint-BasedSimilarity Search StrategiesDissertation zurErlangung des Doktorgrades (Dr. rer. nat.) derMathematisch-Naturwissenschaftlichen Fakult¨at derRheinischen Friedrich-Wilhelms-Universit¨at Bonnvorgelegt vonYuan Wangaus PekingBonn2009Angefertigt mit Genehmigung der Mathematisch-NaturwissenschaftlichenFakult¨at der Rheinischen Friedrich-Wilhelms-Universit¨at Bonn1. Referent: Univ.-Prof. Dr. rer. nat. Jurg¨ en Bajorath2. Referent: Dr. rer. nat. Andreas WeberTag der Promotion: 05 November 2009Erscheinungsjahr 2009AbstractMolecular fingerprints are bit string representations of molecular struc-ture and properties. They are among the most popular descriptors and tools inmolecular similarity searching because of their conceptual simplicity and com-putational efficiency. In order to calculate molecular similarity, fingerprintsare computed for reference and screening database compounds and their bitsettings are quantitatively compared using similarity metrics. One caveat ofthis approach is the bias caused by complexity effects: complex molecules havehigher fingerprint bit density and produce artificially high similarity values.The asymmetric behavior of Tversky similarity measurement has beenreported: comparing A to B is not equal to comparing B to A. This phe-nomenon can be directly attributed to complexity effects.