中文摘要：

首先阐述了分子对接设计的基本原理，然后在蛋白质受体中引入关键残基的概念，建立了一个新的柔性分子对接模型．以配体的中心坐标以及它和受体关键残基的旋转键角为设计变量，以设计变量的尺寸为约束，通过最小化分子间相互作用能得到分子的最优取向和构象．一个自适应的遗传算法被用于求解上述优化模型，该算法采用多种群遗传策略、信息熵控制的空间减缩搜索技术以及拟精确罚函数方法，较好地平衡了效率与精度之间的关系，从而能够快速而稳定地逼近最优解．在此基础上，发展了新的精细分子对接程序，该程序可以进行受体与配体的柔性对接．药物分子对接实例证明，本文发展的精细药物分子对接算法和程序能够有效地用于药物分子设计．

英文摘要：

The basic theory of molecular docking design was first briefly described, and then the concept of the key residues in the protein receptor was introduced to establish a new flexible docking modeS. The optimization problem was to find optimal molecular orientation and conformation by minimizing the intermolecular interaction energy. The Cartesian coordinates of the ligand centre and the torsion angles of the ligand atoms and key residues in the receptor were considered as design variables, and the constraints consisted of the lower and upper bounds on the design variables. An adaptive genetic algorithm in conjunction with multipopulation genetic strategy, entropy-based searching technique with narrowing down space and the quasi-exact penalty function was developed to solve the optimization problem. The proposed method culd successfully balance the efficiency against precision, and close the optimal solution quickly and stability. To be oriented with drug design and development, a new refined molecular docking program had been developed, which considers the flexibility of both the ligand and receptor simultaneously. The docking results showed that the method and program can used in the drug molecular design efficiently.