Dissociation of\nNicotine from Acetylcholine-Binding\nProtein under Terahertz Waves Radiation

The binding of nicotine (NCT) to acetylcholine-binding\nprotein\n(AChBP) plays an important role in synaptic transmission and neurotransmitter\nregulation. However, effectively regulating their binding or dissociation\nprocesses remains a challenging problem. In this study, we employed\nall-atom molecular dynamics (MD) simulations to systematically investigate\nthe impact of external terahertz (THz) waves on the binding kinetics\nbetween AChBP and NCT. We first identified the key residues (i.e.,\nW143) and the key interactions (i.e., hydrogen bonding and cation-π\ninteraction) in AChBP-NCT binding without THz waves. We then investigated\nthe binding and dissociation of charged NCT with AChBP at three different\nfrequencies (i.e., 13.02, 21.44, 42.55 THz). Importantly, the predominant\nvibrational modes at 13.02 THz can drive the rotation of the pentagonal\nring on NCT. This leads to the disruption of hydrogen bonds between\nNCT and W143 and a reduced likelihood of forming cation-π interactions,\nresulting in the dissociation of NCT from AChBP. Additionally, we\nfurther investigated the influence of electric field intensities on\nthe dissociation kinetics and found that when the electric field intensity\nexceeds a critical value (∼0.60 V/nm), the probability of ligand\ndissociation gradually rises as the intensity increases. In general,\nthis study contributes to a better understanding of the effects of\nTHz waves on protein–ligand interactions, which might also\nshed some light on potential applications in nicotine addiction treatment\nand therapeutic strategies for neurodegenerative diseases.