In silico approach of azadirachtin binding with actins

Abstract

In silico docking analysis reported here suggests that insect cellular cytoskeletal β-actin could be the target of Azadirachtin A (Aza—the principle bioactive compound of neem seeds). The best docking energy of −40.09 kcal/mol at 8.73 Å RMSD and predicted hydrogen bond between Arg210 and carboxymethyl group of Aza accompanied with seven hydrophobic interactions in the proposed binding site strongly support this hypothesis. This is of specific interest due to the non-affinity of Aza to mammalian β-actins under the same set of conditions, although β-actins across the species are highly conserved. Our results show that few scattered amino acid changes have caused significant steric hindrance in the binding pocket for mammalian β-actin, causing a reverse orientation of Aza. These results suggest a model to support the recently observed biological effects caused by Aza in Drosophila cytoskeletal elements and explain why Aza is highly specific to insects than mammals.