Aptamer has been applied for detection， separation / purification and clinic fields， because of many advantages such as stability， easy preparation， small molecular weight， simple storage and transportation. The traditional screening method always need complicated procedure and operation， and the mechanism of screening is still unclear. In the paper， based on computer-aided molecular modeling， the binding site of the known aptamer and 5' adenosine monophosphate（AMP） was studied， seven key bases were chosen to further mutate by wheel iteration orientation method. The new sequences were obtained by the comparation of the binding free energy step by step. After the fourth step， there were four new sequences （named as S1-S4） with high specificity were chosen. In the experiment， the best sequence（S4） and the initial sequence （S0） were identified by visual detection using colloidal gold. It was found that the experimental results were well agreement with the modeling results. It provides a basic platform to the optimal screening of the aptamer.