Design of libraries to explore receptor sites

Despite rapid progress in both combinatorial chemistry and high-throughput screening, the number of molecules that could potentially be made and tested for biological activity still far exceeds the capacity for synthesis or screening. Consequently, it is potentially valuable to select and synthesize sublibraries that contain rationally selected subsets. When the structure of the protein receptor site is known, this may be used to impose restrictions of the selection on molecules. This paper describes a method for rapid analysis of large virtual libraries to select a subset that can exhibit at least one conformer which wil interact strongly with the receptor and fit within the receptor site.