Edvardsen O, Dahl S G
Department of Pharmacology, University of Tromosø, Norway.
J Neural Transm Gen Sect. 1991;83(3):157-70. doi: 10.1007/BF01253386.
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.
基于AMBER力场的分子动力学模拟和能量计算被用于研究乙酰胆碱在真空和水溶液中的分子运动及低能构象。乙酰胆碱的电子结构通过从头算量子力学计算得出。从晶体结构获得的三种构象以及之前计算得到的两种构象被用作模拟的起始几何结构。反式、 gauche构象在真空和水溶液中均具有最低能量。在水中的分子动力学过程中观察到了反式、 gauche和反式、反式构象，这表明这两种构象都相对稳定。在水中的分子动力学模拟过程中，乙酰甲基的旋转速度比氮原子处的甲基更快。两种类型甲基的相关时间与核磁共振数据高度吻合，这表明此类模拟为神经递质的分子运动提供了有效的信息。
