蛋白质分子与配体结合过程构象变化的研究

蛋白质分子与配体的作用模式主要有直接的环区结合及铰链式结合两种方式。针对这两种不同的作用方式,我们提出采用不同的策略进行结合过程的构象研究。对于直接的环区结合模式,通过建立环区主链构象库,来实现蛋白质环区与配体的准柔性对接,并以链霉抗生物素蛋白体系为例对构象库建立的可行性进行了验证计算。对铰链结合方式,采用分步对接的方法进行计算,并具体应用于HIV蛋白酶与其小分子配体的结合过程。计算结果表明,这两种处理方法分别能较好地模拟不同类型的蛋白质与配体结合的的构象变化。

Conformational changes acompanying with the binding of protein and ligand

The binding of protein with its ligand can be generalized into two major modes: direct binding with surface loops or binding associated with hinge movement. Two different strategies were developed to study the conformational variation in the binding process. For directive loop binding, a combinatorial conformational library for the backbone structure of the loop was built up, which includes all possible sub - stable conformations of the loop during the binding procedure. The library of conformations was subject to screening by rigid docking. The Streptavidin complex was used as an example to explore the possibility to build the combinatorial conformational library of loop backbone. For hinge binding movement, step - by - step docking method has been proposed and applied to HIV - 1 protease and inhibitor system. The results show that both methods can simulate the conformational variation of proteins in the binding process successfully. The proposed methods for studying the binding process of protein and ligand will be helpful for protein and drug design.