烟碱型乙酰胆碱受体吡啶基胺类配体的构效关系研究

QSAR Studies of Novel Pyridylamine Ligands for the Nicotinic Acetylcholine Receptor

采用分子动力学模拟退火技术寻找了一类新型烟碱型乙酰胆碱受体吡啶基胺类配体分子的优势构象,用分子力学方法进行了结构优化,再用半经验量子化学方法中的AM1方法进一步优化,并做了电子结构计算.用计算所得物化参数对配体亲和性进行多元线性回归分析,回归结果表明:化合物pKi值与分子最低空轨道能量(E_(LUMO))、吡啶基所带总电荷(Q_p)及分子构象相关.根据计算结果对该类化合物与受体的作用机制和作用位点进行了讨论.

Optimized geometries of twenty three pyridylamine ligands for the nicotinic acetylcholine receptor are obtained by using simulated annealing Method of molecular dynamics. Then these complexes are optimized by molecular mechanics and semi-empirical quantum mechanics method-AMI and the electronic structures are calculated. The result reveals that the value of p K-i has some relationship with the energy of lowest unoccupied molecular orbital, charge on the pyridyl group and molecular conformation.