Tryptophan 7-halogenase catalyzes chlorination of free tryptophan to 7-chlorotryptophan, which is the first step in the antibiotic pyrrolnitrin biosynthesis. Many biologically and pharmaceutically active natural products contain chlorine and thus, an understanding of the mechanism of its introduction into organic molecules is important. Whilst enzyme-catalyzed chlorination is accomplished with ease, it remains a difficult task for the chemists. Therefore, utilizing enzymes in the synthesis of chlorinated organic compounds is important, and providing atomistic mechanistic insights about the reaction mechanism of tryptophan 7-halogenase is vital and timely. In this work, we examined a mechanism for the reaction of tryptophan chlorination, performed by tryptophan 7-halogenase, by calculating potential energy and free energy surfaces using two different Combined Quantum Mechanical/Molecular Mechanical (QM/MM) methods both employing Density Functional Theory (DFT) for the QM region. Both computational strategies agree on the nature of the rate-limiting step and provided close results for the reaction barriers of the two reaction steps. The calculations for both the potential energy and the free energy profiles showed very similar geometric features and hydrogen bonding interactions for the characterized stationary points.