title: A Bright Future for Evolutionary Methods in Drug Design.
abstract: Most medicinal chemists understand that chemical space is extremely large, essentially infinite. Although high-throughput experimental methods allow exploration of drug-like space more rapidly, they are still insufficient to fully exploit the opportunities that such large chemical space offers. Evolutionary methods can synergistically blend automated synthesis and characterization methods with computational design to identify promising regions of chemical space more efficiently. We describe how evolutionary methods are implemented, and provide examples of published drug development research in which these methods have generated molecules with increased efficacy. We anticipate that evolutionary methods will play an important role in future drug discovery.
authors.affiliation: Cell Biology Group, Biomedical Materials Program, CSIRO Manufacturing Flagship, Bag 10, Clayton South MDC 3169 (Australia).
authors.forename: Tu C
authors.initials: TC
authors.lastname: Le
authors.affiliation: Cell Biology Group, Biomedical Materials Program, CSIRO Manufacturing Flagship, Bag 10, Clayton South MDC 3169 (Australia). dave.winkler@csiro.au.|Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville 3052 (Australia). dave.winkler@csiro.au.|Latrobe Institute for Molecular Science, Latrobe University, Bundoora 3046 (Australia). dave.winkler@csiro.au.
authors.forename: David A
authors.initials: DA
authors.lastname: Winkler
mesh_terms: D000465:Algorithms; D015195:Drug Design; D055808:Drug Discovery; D021281:Quantitative Structure-Activity Relationship; D052156:SELEX Aptamer Technique
keywords: chemical space; drug design; drug-like space; evolutionary algorithms; genetic algorithms