This paper provides a feasible model for molecular structure analysis and interaction mechanism of aptamer and micromolecule. In this study, modeling and dynamic simulation of ssDNA aptamer (P-18S2) and target (Palytoxin, PTX) were performed separately. Then, the complex structure between DNA and PTX was predicted, and docking results showed that PTX could combine steadily at the groove's top of DNA model by strong hydrogen-bonds and electrostatic interaction. Thus, we truncated and optimized P-18S2 by simulating. At the same time, we also confirmed the reliability of simulation results by experiments. With the experimental and computational results, the study provided a more reasonable interpretation for the high affinity and specific binding of P-18S2 and PTX, which laid the foundation for further optimization and development of aptamers in molecular diagnostics and therapeutic applications.