Computational methods for the integration of biological activity and chemical space [Elektronische Ressource] / vorgelegt von Eugen Lounkine

Computational Methods for theIntegration of Biological Activityand Chemical SpaceDissertation zurErlangung des Doktorgrades (Dr. rer. nat.) derMathematisch-Naturwissenschaftlichen Fakult¨at derRheinischen Friedrich-Wilhelms-Universitat¨ Bonnvorgelegt vonEugen Lounkineaus MoskauBonn2009Angefertigt 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. Michael Gut¨ schowTag der Promotion: 29.10.2009Erscheinungsjahr: 2009For my ParentsAbstractOne general aim of medicinal chemistry is the understanding ofstructure-activity relationships of ligands that bind to biological targets. Ad-vances in combinatorial chemistry and biological screening technologies allowthe analysis of ligand-target relationships on a large-scale. However, in order toextractusefulinformationfrombiologicalactivitydata,computationalmethodsare needed that link activity of ligands to their chemical structure.In this thesis, it is investigated how fragment-type descriptors of molec-ular structure can be used in order to create a link between activity and chem-ical ligand space. First, an activity class-dependent hierarchical fragmentationscheme is introduced that generates fragmentation pathways that are alignedusing established methodologies for multiple alignment of biological sequences.