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Before performing the DNA computation, a set of specific DNA sequences are required. However, this is a burdensome task as too many constraints need to be satisfied. In this paper, ant colony algorithm is applied to solve the problem of DNA codewords design. Inspired by the traveling salesman problem, first a city matrix with T rows and S columns is designed, in which every city denotes a DNA sequence. Then the artificial ants begin to search for an optimal route based on the DNA thermodynamic and combinational constraints. At last, the shortest rout with S sequences is the desired set of DNA codewords. The simulation results of the proposed approach shows better convergency and can provide reliable and effective codewords for the controllable DNA computation.