Exploring binding mechanism of naringenin to human transferrin using combined spectroscopic and computational methods: Towards therapeutic targeting of neurodegenerative diseases

Abstract

Excessive iron deposition is linked to the pathology of neurodegenerative, signifying the importance of iron homeostasis. Together with ferritin, human transferrin (hTf) play significant roles in iron homeostasis. Naringenin (Nag) is a flavanone known to have neuroprotective action. Inhibition of hTf, which reduces the free iron, is an attractive strategy to treat neurodegenerative diseases. This study explores the binding of Nag to hTf employing in-silico and in vitro approaches. Molecular docking studies deciphered binding of Nag to hTf with a high affinity through metal coordination bonding. Further, 200 ns all-atom molecular dynamic simulation studies were performed to understand the hTf-Nag complex dynamics. No significant structural alterations occur in hTf upon binding of Nag, suggesting the stability of the hTf-Nag complex. Computational studies were supported by experimental methods. Fluorescence binding studies suggested that Nag binds to hTf with an excellent affinity. Isothermal titration calorimetric studies further validated the spontaneous nature of binding of Nag to hTf and provided various thermodynamic parameters of the hTf-Nag complex. The present work provides a platform to use Nag in therapeutic strategies to manage neurodegenerative disorders. © 2022 Elsevier B.V.