The impact of caffeine on tau-tau interaction: LSPR detection, structural modification and molecular dynamics simulation

Abstract Protein-protein interactions are involved in many biological processes and cellular functions and they are interesting therapeutic targets is several diseases for drug design and development. In the present study, the possible effects of caffeine (CF) as mostly consumed psychoactive substances in the modern life on tau-tau interactions were studied by localized surface plasmon resonance (LSPR) method. The obtained data indicated that tau monomers have high affinity to bind to the immobilized tau proteins on the surface of LSPR sensor chip of the gold nanoparticles (LSPR-AuNPs) and the LSPR peak was red-shifted from 598 ± 1.5 nm to 629 ± 0.1 nm. However, it was shown that the binding affinity of CF-tau complex was remarkably reduced. These results revealed that the binding of CF molecules on free tau monomers could potentially interrupt the interaction of tau-tau proteins. Circular dichroism (CD) and FTIR spectroscopy was applied to analyze the secondary structure of tau protein in the absence or presence of different amounts of CF. The results showed that CF can induce more random coil structure to the protein and also increase its structural stability. Docking studies and molecular dynamics simulations elucidated that CF not only can possibly provide a molecular and physical barrier for tau-tau interaction by binding to the microtubule binding domain, but also it decreases the stability of tau dimer, which were supported by experimental data.