Rational Screening Set Design and Compound Selection: Cascaded Clustering

Abstract

The use of cascaded clustering is reported. This technique was developed to permit the application of Jarvis-Patrick clustering based on structural fingerprints to large chemical databases, while keeping the maximum cluster size and the number of singletons produced at reasonable levels. The basis for the algorithm, its implementation, and validation are described. In the first part of the paper, the approach is used to create a representative subset of compounds for biological testing from the corporate compound repository. A variation of the method is then used for the comparison of relatively large databases. Finally, compound selection using cascaded clustering is shown to be complementary to the Diverse Property-Derived approach, which is based on partitioning by six molecular descriptors.