Molecular Docking Studies on the Interactions of Human Farnesyl Pyrophosphate Synthase with α-Aminobisphosphonates Compounds

Abstract

The nitrogen-containing bisphosphonates (N-BPs) are a major class of drugs for the treatment of diseases characterized by excessive bone resorption. Farnesyl pyrophosphosphate synthase (FPPS), one of the key enzymes involved in the mevalonate pathway, is the major molecular target of N-BPs. From the comparative docking study of our compounds with many structurally related lead compounds such as zoledronate and pamidronate we could observe how our compounds might bind to the FPPS binding site, based on the knowledge of the structure of similar active sites. We redocked zoledronate and pamidronate into the active site of the enzyme, and then we replaced with our compounds in order to compare the binding mode of both ligand and the test compound.