Abstract: An improved mixed genetic simulated annealing algorithm (MGASA) was presented，which combined the advantages of GA and SA，and avoided the problem of combination explosion. A new category style was adopted，and the stability and integrity of molecule can be judged easily. That resolved the problem of molecular combination. The results of an example showed that the fitness values were larger than those in literature. The CAMD method in this paper has a high level of accuracy and can be used in practical chemical processes.