关键词: 生物碱, 从头计算法, 石杉碱甲

The difference between Huperzine A (HupA) structure in Acetylcholinesterase (AChE)-HupA complex and the structure in gase phase has been studied by using ab initio method of quantum chemistry. The model system composed of 410 atoms abstracted from the active site of HupA-AChE complex and of the 1929 point charges around the 410 atoms was calculated employing HF/4-31G method. The HupA itself in gase phase state was optimized with HF/4-31G. The calculation result indicated that the binding conformer and the global minimal energy conformer of HupA is 91.8kJ/mol. The changes of LUMO and HOMO energies indicate that the electrons were transferred between AChE and HupA. Great changes have been taken palce for the total atomic charge, bond lengthes and orientations of some of the atoms and bonds in HupA when it binds to the AChE: the C=O and N-H bond of amide group and the N-H bond of the amino group of HupA have been elongated and weakened in HupA-AChE complex, the torsion angle of bond C(3)-C(8)-N(21)-H(35) alters even about 20ⅲ. These changes are caused by the hydrogen bonds formation between HupA and AChE. All of these are useful clues for designing novel huperzine A analogs to inhibite the activity of acetylcholinesterase.

Key words: ALKALOID, AB INITIO CALCULATION