Abstract
Natural products are made by nature through interaction with biosynthetic enzymes.
They also exert their effect as drugs by interaction with proteins. To address the
question “Do biosynthetic enzymes and therapeutic targets share common mechanisms
for the molecular recognition of natural products?”, we compared the active site of
five flavonoid biosynthetic enzymes to 8077 ligandable binding sites in the Protein
Data Bank using two three-dimensional-based methods (SiteAlign and Shaper). Virtual
screenings efficiently retrieved known flavonoid targets, in particular protein kinases.
A consistent performance obtained for variable site descriptions (presence/absence
of water, variable boundaries, or small structural changes) indicated that the methods
are robust and thus well suited for the identification of potential target proteins
of natural products. Finally, our results suggested that flavonoid binding is not
primarily driven by shape, but rather by the recognition of common anchoring points.
Key words
flavonoid - biosynthetic enzyme - natural product - binding site similarity
