Refined molecular docking method considering protein flexibility

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 model. 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 multi-population 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 could 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.