Molecular structure and dynamics of acetylcholine.

Molecular dynamics simulations and energy calculations based on the AMBER force field were used to examine the molecular movements and low-energy conformations of acetylcholine in vacuum and in aqueous solution. Electronic structures of acetylcholine were calculated by ab initio quantum mechanical calculations. Three conformations obtained from crystal structures and two from previous calculations were used as starting geometries in the simulations. The trans, gauche conformer had lowest energy both in vacuum and in aqueous solution. Both trans, gauche and trans, trans conformers were observed during molecular dynamics in water, which indicates that both conformations are relatively stable. The acetyl methyl group rotated more rapidly than those at the nitrogen atom during molecular dynamics simulations in water. Correlation times of both types of methyl groups were in good agreement with NMR data, which demonstrates that such simulations provide valid information about molecular movements of the neurotransmitter.