Waldmann has developed a new concept for the design
of combinatorial libraries based on natural products that he
calls BIOS.154-156 This concept is based on the recognition
of fundamental and complementary properties of natural products and their protein targets. Nature, through evolution
of natural products, has explored only a tiny fraction of the
available small-molecule chemical space. The same holds
true for the biological targets of natural products, which are
mainly proteins. The number of three-dimensional protein
folds have been shown to be even more conserved during
evolution than the underlying sequences, since topologically
similar shapes can be formed by different sequences