Scaffold tree

Schuffenhauer, A. et al. 2007. Scaffold tree visualization of the scaffold universe by hierarchical scaffold classification. J. Chem. Inf. Model. 47,47-58. 

These two approaches, the scaffold tree as applied in SCONP as well as PSSC, are introduced and exemplified by selected applications in the following sections. We also demonstrate first applications of BIOS which successfully combine chemistry and biology. 

B. The scaffold tree for structural classification of natural products... 

This procedure led to a unique, hierarchical classification of scaffolds, in which each scaffold in the hierarchy is a well-defined chemical entity, which is a substructure of the original molecules. Thereby more complex scaffolds can be reduced to smaller scaffolds aeating branches and several branches merge toward the inner circles of the tree. This procedure leads to a reduction of molecular complexity from multiple annulated rings at the outer rims to single ring systems at the most inner circle of the scaffold tree (Figure 9.10). 

FIGURE 9.11 A selection of important rules guiding the most recent scaffold tree generating algoridim. 

FIGURE 9.12 Structural motifs identified in the natural product scaffold tree and used as templates for natural product-based compound collections. 

For compound sets with a well defined limit, it is possible to enumerate all the scaffolds in the set and to visualise the chemical relationships. In particular, the Bioactivity guided Scaffold tree method (BIOS) provides a visually compelling means of exploring complex structural relationships. As an example, the Structural Classification of Natural Products (SCONP) arranges the scaffolds of the natural products in this tree-like fashion. This provides a concise and chemistry friendly description of natural product diversity. 

Figure 14.2 The Scaffold tree visualisation of the Structural Classification of Natural Products (SCONP). Reproduced from ref. 61, Waldman et al., Proc. Natl. Acad. Sci. 2005, 102, 17272. Copyright 2005 National Academy of Sciences, U.S.A.

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