Dissociation of Nicotine from Acetylcholine-Binding Protein under Terahertz Waves Radiation.

The binding of nicotine (NCT) to acetylcholine-binding protein (AChBP) plays an important role in synaptic transmission and neurotransmitter regulation. However, effectively regulating their binding or dissociation processes remains a challenging problem. In this study, we employed all-atom molecular dynamics (MD) simulations to systematically investigate the impact of external terahertz (THz) waves on the binding kinetics between AChBP and NCT. We first identified the key residues (i.e., W143) and the key interactions (i.e., hydrogen bonding and cation-π interaction) in AChBP-NCT binding without THz waves. We then investigated the binding and dissociation of charged NCT with AChBP at three different frequencies (i.e., 13.02, 21.44, 42.55 THz). Importantly, the predominant vibrational modes at 13.02 THz can drive the rotation of the pentagonal ring on NCT. This leads to the disruption of hydrogen bonds between NCT and W143 and a reduced likelihood of forming cation-π interactions, resulting in the dissociation of NCT from AChBP. Additionally, we further investigated the influence of electric field intensities on the dissociation kinetics and found that when the electric field intensity exceeds a critical value (∼0.60 V/nm), the probability of ligand dissociation gradually rises as the intensity increases. In general, this study contributes to a better understanding of the effects of THz waves on protein-ligand interactions, which might also shed some light on potential applications in nicotine addiction treatment and therapeutic strategies for neurodegenerative diseases.