Novel methodologies for investigation of nuclear quantum effects in hydrogen transfer reactions

Two theoretical methods allowing efficient computational modeling of proton transfer reactions are presented. The first method, denoted partial mulidimensional grid generation, is useful in grid-based mixed quantum-classical molecular dynamics simulations. The second approach, denoted the nuclear-electron orbital (NEO) method, incorporates nuclear quantum effects into electronic structure calculations with molecular orbital techniques.; The partial multidimensional grid generation method decreases the number of potential energy calculations in grid-based simulations by avoiding points with high potential energy. The application of this method to the calculation of three-dimensional hydrogen nuclear wave functions in the enzyme liver alcohol dehydrogenase is presented. The results indicate that the partial multidimensional grid generation method is nearly as accurate as and significantly faster than the standard full grid method.; In the nuclear-electronic orbital approach selected nuclei are treated quantum mechanically with molecular orbital techniques. Both electronic and nuclear molecular orbitals are expressed as linear combinations of Gaussian basis functions. The advantages of the NEO approach are that nuclear quantum effects are incorporated during the electronic structure calculation, the Born-Oppenheimer separation of electrons and nuclei is avoided, excited vibrational-electronic states may be calculated, and its accuracy may be improved systematically. Single configurational as well as multiconfigurational NEO approaches are presented. The derivations of the analytic gradient expressions are presented for both NEO-HF (Hartree-Fock) and NEO-MCSCF (multiconfigurational self-consistent-field). These analytic gradients allow the variational optimization of the centers of the nuclear basis functions and the location of geometry stationary points. The methodology for a vibrational analysis within the NEO framework is also presented. The vibrational analysis enables the characterization of geometry stationary points, as well as the calculation of zero point energy corrections and thermodynamic properties. Initial applications are presented to illustrate the computational feasibility and accuracy of this approach.