一种考虑蛋白质柔性的分子对接方法

分子对接是计算机辅助药物分子优化设计中的一种重要方法,为此建立了基于诱导契合的分子对接优化模型.模型中引入残基基团的概念,将蛋白质划分成若干个残基基团,通过这些残基基团的运动近似表征整个蛋白质的运动情况,并将配体小分子的运动处理为平移、转动和柔性键旋转三部分分量.设计了一个将k-均值聚类和遗传算法相结合的快速迭代格式,并采用多种群遗传策略和信息熵控制的空间减缩搜索技术加速了分子对接设计中的遗传演化进程.在此基础上,开发了一种考虑蛋白质柔性的对接程序FkxGAsDock.数值试验表明,该程序较好地平衡了效率与精度之间的关系,取得了满意的对接结果.

A molecular docking method considering protein flexibility

Molecular structural optimization is an invaluable tool in computer-aided molecular design. A new flexible docking optimization model based on induced-fit interaction is proposed. In the model, a concept of residue groups is introduced to describe the protein movement approximately and the movement of ligand is described by the translation, votation and torsion motions. A new iteration scheme in conjunction with the \%k\%-means clustering algorithm and genetic algorithm is developed to solve the optimization model for the molecular docking. Multi-population genetic strategy and entropy-based searching technique with narrowing down space are employed in the method, making the efficiency of genetic evolution very high. A new docking program FlexGAsDock considering the protein flexibility has been developed. The docking results show that the method can be used in the drug molecular design efficiently.