探索应用反向对接技术研究蛋白激酶抑制剂选择性的可行性

本文探索了应用反向对接技术研究激酶抑制剂选择性的可行性。首先通过收集晶体结构数据或使用同源建模方法建立了包含422个激酶的靶点三维结构数据库, 在此基础上建立了反向对接激酶靶点筛选方法, 并对相关参数和打分函数进行了优选。最后, 选取了7个典型的选择性激酶抑制剂作为例子, 用于测试该反向对接激酶靶点筛选方法。结果表明, 这些激酶抑制剂的选择性作用靶点均具有较高的打分值 (打分值均排在所测试激酶的35% 以内)。本文的研究提示, 反向对接技术可以应用于激酶靶点虚拟筛选, 并进而应用于激酶抑制剂的选择性研究。

The feasibility of application of reverse docking method to the selectivity studies of protein kinase inhibitors

This investigation is to explore the feasibility of applying reverse docking method to the selectivity studies of protein kinase inhibitors.  Firstly, a database that consists of 422 protein kinase structures was     established through collecting the reported crystal structures or homology modeling.  Then a reverse docking based method of protein kinase target screening was established, followed by the optimization of related parameters and scoring functions.  Finally, seven typical selective kinase inhibitors were used to test the established method.  The results show that the selective targets of these inhibitors have relatively high scoring function values (ranking in the first 35% of the tested kinase targets according to the scoring function values).  This implies that the   reverse docking method can be applied to the virtual screening of kinase targets and further to the selectivity studies of protein kinase inhibitors.