Molecular structure and dynamics of acetylcholine

Abstract

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.

A kinetic and allosteric model for the acetylcholine transporter-vesamicol receptor in synaptic vesicles

“…The conformations of AcCh and the chimera were energy-minimized about the probable conformation of AcCh bound to the transporter that was determined by . This trans-trans conformer for AcCh is observed during molecular dynamics in water, indicating that it indeed is relatively stable (Edvardsen & Dahl, 1991). The resulting energy-minimized structures are superimposed in Figure 7.…”

Ab initio and DFT computer studies of complexes of quaternary nitrogen cations: trimethylammonium, tetramethylammonium, trimethylethylammonium, choline and acetylcholine with hydroxide, fluoride and chloride anions

“…1(e) is acetylcholine fluoride and Table 1 includes complexes possessing a plane of symmetry and a trans,trans conformation about the two C-O and C-C dihedral arrangements for the central -O-CH 2 -CH 2 -molecular backbone. Here other conformations have been described and reviewed, 1,2 Properties of different conformers will be considered in Section 4 of the present paper.…”

“…One group of such fragments are the ATA's (alkyltrimethylammonium compounds) of which an important example is acetylcholine. This has been the subject of molecular dynamics and ab initio studies in relation to its neurotransmitter properties by Edvardsen and Dahl 1 and for which a deficiency in the brain is associated with Alzheimer's disease. These authors concluded that both trans,trans and trans,gauche conformers for the respective central backbone C-O and C-C bonds were present in the free state and in aqueous solution with the trans,gauche form having the lowest energy.…”

A Density-Functional Study of the Conformational Preference of Acetylcholine in the Neutral Hydrolysis

“…The five ACh + conformers (tg * g, tgg, ttg, tgt, and ttt) are in the low-level group (Figure 3a-e), and the other two conformers (ctg and ctt) are in the high-level group (Figure 3f,g). Other computational studies [20,23,39,40] also conclude the stability of the five low-level conformers. It is important to note that our results support the experiments that observed ACh + (tg * g), (tgg), and (ttg) in their stable states [29,41,42].…”