论文部分内容阅读
应用了一种新的预测酶－配体复合物亲和性的方法来研究凝血酶抑制剂的结构－活性关系．凝血酶－抑制剂复合物的三维结构根据模板化合物的晶体结构进行搭建，然后使用程序SCORE计算复合物的亲和性．共分析了3个系列34个抑制剂分子．计算所得的复合物的解离常数与实验值吻合得很好，大大优于用分子力学所给出的结果．通过比较其中两个抑制剂分子的结构和活性，说明了此方法能够定量给出配体分子中每个原子对结合过程的贡献大小，给出十分直接的结构－活性关系．
A new predictive enzyme-ligand complex affinity assay was used to study the structure-activity relationship of thrombin inhibitors. The three-dimensional structure of the thrombin-inhibitor complex was built according to the crystal structure of the template compound, and then the program affinity was calculated using the program SCORE. Three series of 34 inhibitor molecules were analyzed. The calculated dissociation constants of the complexes are in good agreement with the experimental data, which is much better than the results given by molecular mechanics. By comparing the structure and activity of two inhibitor molecules, it is shown that this method can quantitatively give the contribution of each atom in the ligand molecule to the binding process, giving a very direct structure-activity relationship.