Comprehensive insight into the molecular interaction of rutin with human transferrin: Implication of natural compounds in neurodegenerative diseases

Neurodegeneration, a process of irreversible neuronal damage, is characterized by a damaged neuronal structure and function. The interplay between various proteins maintains homeostasis of essential metals in the brain, shielding neurons from degeneration; human transferrin (Htf) is essential in maintaining iron homeostasis. Any disruption in iron homeostasis results in the development of neurodegenerative diseases (NDs) and their pathology, mainly Alzheimer's disease (AD). Rutin is a known compound for its neuroprotective effects. In this work, we deciphered the binding of rutin with Htf in a bid to understand the interaction mechanism. The results of fluorescence and UV–vis spectroscopy demonstrated strong interaction between rutin and Htf. The enthalpy change (∆H°) and entropy change (∆S°) analysis demonstrated hydrophobic interactions as the prevalent forces. The binding mechanism of rutin was further assessed atomistically by molecular docking and extensive 200 ns molecular dynamic simulation (MD) studies; molecular docking showed binding of rutin within Htf's binding pocket. MD results suggested that binding of rutin to Htf does not cause significant structural switching or disruption of the protein's native packing. Overall, the study deciphers the binding of rutin with hTf, delineating the binding mechanism and providing a platform to use rutin in NDs therapeutics.