We hypothesize that the aptamers used in this research will show specific binding interactions with the nucleolin protein, Figure . This innovative approach, explored in the current work, involves first predicting the tertiary structures of DNA-based aptamers and then performing molecular docking simulations. The nucleolin-aptamer interactions are explained based on the surface electrostatics and shape complementary. These results were further validated by experimental work performed in the previous study. Finally, we have also performed aptamer mutations, out of which aptamer APT-M1 and APT-M2 has stronger interactions from the wt aptamers. The current results will help develop novel bacterial-based cancer-targeted therapy.