Trends in virtual combinatorial library design.
Recent developments in combinatorial molecular design using virtual screening methods are summarised. These include similarity-based compound clustering techniques, structure-based docking and scoring, and fragment-based de novo design. Three major trends have been identified: i) the design of small target-focused compound libraries yielding activity-enriched sets of molecules; ii) advanced prediction methods for "drug-like" molecular properties complement activity predictions in the library design process, forming a multi-dimensional objective function; iii) "cherry picking" of selected products is increasingly used in lead generation and optimisation compared to purely educt-driven library design methods aiming at maximising structural diversity.
Schneider
Gisbert
G
Johann Wolfgang Goethe-Universität, Beilstein Professor of Cheminformatics, Institut für Organische Chemie und Chemische Biologie, Marie-Curie Str., Frankfurt, 11, D-60439, Germany. G.Schneider@chemie.uni-frankfurt.de
D000465:Algorithms; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008958:Models, Molecular; D014584:User-Computer Interface