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

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. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study investigates the binding of naringenin (Nag) to human transferrin (hTf) using computational and experimental methods. The results demonstrate that Nag binds to hTf with a high affinity through metal coordination bonding without causing significant structural alterations to hTf. Fluorescence binding and isothermal titration calorimetry studies further confirm the binding nature and thermodynamic parameters of the hTf-Nag complex. These findings provide a potential strategy and platform to utilize Nag in the treatment of neurodegenerative disorders.