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.