The obtained profiles were corrected with the energy spline function defined in terms of interpolated corrections . Single point calculations were performed at B3LYP/6-311++G(2d,2p)/AMBER level of theory, for geometries used for initial structures for QM/MM MD simulations. After that, stationary state structures were optimized with the Baker algorithm and using the micro-macro iteration scheme at AM1/AMBER and B3LYP/6-31G(d,p)/AMBER levels of theory. Every optimized structure was verified by calculating the Hessian and checking the number of imaginary frequencies. Kinetic isotope effects (KIEs) for DHT and 17-MT were calculated from the definition of the free energy of a state . For each of the stationary states, E:S, TS1, E:I, and TS2, three structures were optimized. Then KIEs for every elementary step were calculated as described elsewhere .