Similar interactions of natural products with biosynthetic enzymes and therapeutic targets could explain why nature produces such a large proportion of existing drugs

Abstract

Natural products are made by nature through interaction with biosynthetic enzymes. Natural products also exert their effect as drugs by interaction with proteins. Does the recognition of the natural product by biosynthetic enzymes translate to recognition of the therapeutic target? Molecular modelling of flavonoid biosynthetic enzymes and kinases with a series of natural product kinase inhibitors led to the development of the concept of Protein Fold Topology (PFT). PFT describes cavity recognition points unrelated to protein fold similarity. The topology or spatial properties are preserved even though there is deformation of the protein elements that participate in the protein-ligand interactions. We observe helices or b-strands as equivalent in providing the invariant topology for protein-ligand interaction. In this Highlight, we explore the question: Will PFT aid drug discovery or is it the reason natural products have drug properties?