Interaction of donepezil with tau protein: Insights from surface plasmon resonance and molecular modeling methods

Alzheimer's is a progressive neurodegenerative disease in which extracellular precipitation of amyloid fibrils of the beta peptides and the accumulation of phosphorylated tau in neurofibrillary tangles play major roles. There is some indirect evidence indicating the potential of donepezil to interact with tau protein. In the present study, various aspects of donepezil binding to tau protein have been investigated using surface plasmon resonance (SPR) and molecular modeling methods. Tau protein was immobilized on Au chip using 11-mercaptoundecanoic acid (MUA) and the interaction of various concentrations of donepezil with the immobilized tau was evaluated by SPR at different temperatures. Besides, to have a better understanding of this interaction, molecular docking approach was also performed. The equilibrium constant decreased following increasing the temperature in the presence of various concentrations of donepezil, which indicates that donepezil binding to tau protein increases upon rising temperature. The calculated thermodynamic parameters showed that the main force involved in the interaction is van der Waals and hydrogen bonding. Finally, the molecular modeling analysis showed that donepezil bind to a cavity on R2 region-microtubule binding domain of tau monomer. (c) 2021 Published by Elsevier B.V.