Adaptive combinatorial design of focused compound libraries.
Low-throughput screening for bioactive substances often represents the only way to discover new ligands of a drug target. This limits the number of compounds that can be tested for bioactivity. In such a situation, the design of small, focused compound libraries provides an alternative to the concept of large, maximally diverse screening collections. We present the technique of "adaptive" compound library design, which implements a simulated evolutionary process. Compound assembly and determination of bioactivity can be performed using computer-based methods (virtual screening), or in the laboratory. We show that there exists an optimal combination of the size of a screening library and the number of iterative screening rounds with the aim to keep experimental efforts at a minimum.
Schneider
Gisbert
G
Institute of Organic Chemistry and Chemical Biology, Goethe-University, Frankfurt am Main, Germany.
Schüller
Andreas
A
D000465:Algorithms; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism
D054852:Small Molecule Libraries