IBM and NeSC workshop on Protein Science
National e-Science Centre, Edinburgh, March
15-16 2002
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Hybrid approach for including electronic and nuclear
quantum effects in molecular dynamics simulations of hydrogen transfer reactions
in enzymes and other systems Salomon R. Billeter(+,*), Simon P. Webb(*), Tzvetelin T. Iordanov(*),Pratul K. Agarwal(*), and Sharon Hammes-Schiffer(*) (+) IBM Research, Zurich Research Laboratory, 8803 Rüschlikon, Switzerland (*) Department of Chemistry, Pennsylvania State University, University Park PA 16802, USA A hybrid approach for simulating proton and hydride transfer reactions in enzymes is presented. The electronic quantum effects are incorporated with an empirical valence bond model. The nuclear quantum effects of the transferring hydrogen are included with a mixed quantum/classical molecular dynamics method in which the hydrogen nucleus is described as a multidimensional vibrational wavefunction. The free energy profiles are obtained as functions of a collective reaction coordinate. A perturbation formula is derived to incorporate the vibrationally adiabatic nuclear quantum effects into the free energy profiles. The dynamical effects are studied with the molecular dynamics with quantum transitions (MDQT) surface hopping method, which incorporates nonadiabatic transitions among the adiabatic hydrogen vibrational states. The MDQT method is combined with a reactive flux approach to calculate the transmission coefficient and to investigate the real-time dynamics of reactive trajectories. This hybrid approach includes nuclear quantum effects such as zero point energy, hydrogen tunneling, and excited vibrational states, as well as the dynamics of the complete enzyme and solvent. The nuclear quantum effects are incorporated during the generation of the free energy profiles and dynamical trajectories rather than subsequently added as corrections. Moreover, this methodology provides detailed mechanistic information at the molecular level and allows the calculation of rates and kinetic isotope effects. An initial application of this approach to the enzyme liver alcohol dehydrogenase (LADH) is also presented. |
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