BIOS is based upon two concepts previously developed
by the Waldmann group. The scaffolds of natural products
can be mapped in a hierarchical manner to create a scaffold
tree,a“structuralclassificationofnaturalproducts”(SCONP).170,171
This allows for logical pathways for the structural simplification
of scaffolds. In the second concept, “protein structure
similarity clustering” (PSSC), proteins are clustered by threedimensional
shape around the ligand-binding sites, regardless
of sequence similarity.172-174 Merging these two concepts
led to the BIOS approach.156 The ligand of any member of
a PSSC could be expected to exhibit some degree of
complementarity toward other members of the PSSC and,
thus, serve as a starting point for the development of
modulators of the other members