Intuitive ordering of scaffolds and scaffold similarity searching using scaffold keys.

Scaffold Keys-scaffold descriptors based on simple topological parameters such as number of ring and chain atoms, number and type of heteroatoms, and other simple structural features-are presented. Scaffold Keys enable intuitive ordering of scaffolds from small and simple to large and complex, ordering that is consistent with the way medicinal chemists themselves classify scaffolds. Scaffold Keys may be also used as descriptors for scaffold similarity searches, providing results compatible with expectations of chemists and well-suited for use in scaffold bioisosteric replacement and scaffold hopping. Scaffold Keys also support visualization of large chemical data sets. Scaffold Keys descriptors are easy to understand by chemists as well as easy to implement.