High-Resolution NMR Characterization of the Molecular Interplay between α-Synuclein, Fasudil, and Calcium Ions

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful technique for characterizing the interaction between IDPs and various binding partners at atomic resolution in physiological conditions. In this study, we investigate the interaction between α-syn and fasudil, a compound known to interact with the C-terminal part of α-syn and to delay the formation of its toxic aggregates.2 We also examine the modulatory role of calcium ions in this interaction. For our study we used high-resolution NMR spectroscopy, exploiting both 13C and 1H detected experiments, supported by molecular dynamics simulations, to characterize the interactions between a C-terminal α-syn construct (C-α-syn), the small molecule fasudil, and calcium ions. Our study focuses on the side chains of aspartic acid, glutamic acid, and tyrosine residues, which play a key role in Fasudil and calcium ions binding. We analyze their behavior in the presence and absence of calcium ions to elucidate calcium’s influence in this process.