title: Voyages to the (un)known: adaptive design of bioactive compounds.
abstract: De novo drug design has emerged as a valuable concept for the rapid identification of lead structure candidates. In particular, fragment-based molecular assembly methods have been successfully employed for the automated design of screening compounds. Here, we review the current status of these approaches, with an emphasis on adaptive techniques that can be used to artificially evolve novel bioactive molecules. Evolutionary algorithms (EAs) and particle swarm optimization (PSO) are presented as preferred techniques for iterative virtual synthesis and testing. By the inclusion of straightforward synthesis rules, druglike compounds can be obtained. Evolving compound libraries are particularly suited for hit and lead finding in situations where resources are limited and the complete testing of a large screening compound collection is prohibitive.
authors.affiliation: Johann Wolfgang Goethe-University, Institute of Organic Chemistry and Chemical Biology, LiFF, Siesmayerstr. 70, D-60323 Frankfurt am Main., Germany. g.schneider@chemie.uni-frankfurt.de
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Markus
authors.initials: M
authors.lastname: Hartenfeller
authors.forename: Michael
authors.initials: M
authors.lastname: Reutlinger
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Tanrikulu
authors.forename: Ewgenij
authors.initials: E
authors.lastname: Proschak
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
mesh_terms: D000465:Algorithms; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*
chemical_list: D004364:Pharmaceutical Preparations