Producing DFT/MM enzyme reaction trajectories from SCC-DFTB/MM driving forces to probe the underlying electronics of a glycosyltransferase reaction.

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The SCC-DFTB/MIO/CHARMM free energy surface for a glycosyltransferase, TcTS, is benchmarked against a DFT/MM reaction trajectory using the same CHARMM MM force field ported to the NWChem package. The popular B3LYP functional, against which the MIO parameter set was parameterized is used to optimize TS structures and run DFT reaction dynamics. A novel approach was used to generate reaction forces from a SCC-DFTB/MIO/CHARMM reaction surface to drive B3LYP/6-31G/MM and B3LYP/6-31G(d)/MM reaction trajectories. Although TS structures compare favorably, differences stemming primarily from a minimal basis set approximation prevented a successful 6-31G(d) FEARCF reaction dynamics trajectory. None the less, the dynamic evolution of the B3LYP/6-31G/MM-computed electron density provided an opportunity to perform NBO analysis along the reaction trajectory. Here, we illustrate that a successful ab initio reaction trajectory is computationally accessible when the underlying potential energy function of the semi-empirical method used to produce driving forces is sufficiently close to the ab initio potential. © 2017 Wiley Periodicals, Inc.