Topological Fragment Index for the Analysis of Molecular Substructures and Their Topological Environment in Active Compounds

Abstract

We report the development and application of the Topological Fragment Index (ToFI), a measure for the complexity of the topological environment of defined molecular fragments in active compounds. On the basis of ToFI calculations, RECAP fragments are organized in dependency hierarchies that capture fragment co-occurrence and facilitate the identification of topology clusters and activity class characteristic RECAP fragments. By combining structural and topological environment information through ToFI, RECAP fragments that are a signature of compounds active against one of several closely related targets are consistently identified.