Magic Rings: Navigation in the Ring Chemical Space Guided by the Bioactive Rings

The large majority of bioactive molecules contain a more or less complex ring system as a central structural element. This central core determines the basic molecule shape, keeps substituents in their proper positions, and often also contributes to the biological activity itself. In this study the ring systems extracted from one billion molecules are processed and differences between rings from bioactive molecules and common synthetic molecules are analyzed. The bioactive rings seem to be distributed throughout the large portion of chemical space, but not uniformly; one can see several more dense regions, where the bioactive rings often appear in small clusters, as well as empty areas. A web tool offering an interactive navigation in the ring chemical space and supporting identification of bioisosteric ring analogs available at https://bit.ly/rnagicrings is also described.

Automated summary

In this study, the differences between ring systems from bioactive molecules and common synthetic molecules are analyzed by processing the ring systems extracted from one billion molecules. The bioactive rings are found to be distributed throughout the chemical space, but not uniformly, with several dense regions and empty areas. Additionally, a web tool for interactive navigation and identification of bioisosteric ring analogs in the ring chemical space is described.