Sharon Hammes-Schiffer

Theory and Simulation of Charge Transfer Reactions

Charge transfer reactions play a vital role in a wide range of chemical and biological processes. Professor Hammes-Schiffer's research centers on the theoretical and computational investigation of charge transfer reactions. This research combines the development of new theoretical and computational methods with applications to chemically and biologically important reactions. The types of processes studied include multiple proton transfer, proton-coupled electron transfer, and hydride transfer reactions in solution and in proteins. The goal of this research is to elucidate the charge transfer mechanisms and to predict rates and kinetic isotope effects for comparison to experiment.

One major focus of the Hammes-Schiffer group is the development of a hybrid approach for the quantum-classical molecular dynamics simulation of proton and hydride transfer reactions in enzymes. This approach includes electronic and nuclear quantum effects, as well as the motion of the entire solvated enzyme. It allows the calculation of rates and kinetic isotope effects for comparison to experiment. Applications of this hybrid approach to biochemically important enzyme reactions have elucidated the importance of the nuclear quantum effects such as hydrogen tunneling and have provided insight into the fundamental relation between enzyme motion and catalytic activity. In particular, these simulations have provided evidence of a network of coupled motions extending throughout the protein and ligands. These motions represent conformational changes along the collective reaction coordinate for hydride transfer and give rise to conformations in which the hydride transfer reaction is facilitated. Simulations of a mutant DHFR enzyme are consistent with the experimental rate measurements and indicate that a mutation far from the active site may modify the network of coupled motions through structural perturbations, thereby increasing the free energy barrier and decreasing the reaction rate. These concepts have important implications for protein engineering and drug design.

A second focus of the Hammes-Schiffer group is the development of a theoretical formulation for proton-coupled electron transfer (PCET) reactions, which are vital to many chemical and biological processes. In this theory, the active electrons and transferring proton are treated quantum mechanically. Analytical expressions have been derived for the free energy surfaces and rates. This theory elucidates the fundamental chemical and physical principles of PCET reactions and provides predictions of the dependence of the rates, mechanisms, and kinetic isotope effects on the physical properties of the solute and the solvent. Applications of this theory to chemically and biologically important PCET reactions have aided in the interpretation of experimental results.

A third focus of the Hammes-Schiffer group is the development of the multiconfigurational nuclear-electronic orbital method for including nuclear quantum effects in electronic structure calculations. Both electronic and nuclear molecular orbitals are expressed as linear combinations of Gaussian basis functions, and the variational method is utilized to minimize the energy with respect to all molecular orbitals. Correlation effects are included using multiconfigurational self-consistent-field and many-body perturbation theory approaches. For hydrogen transfer reactions, the transferring hydrogen nuclei, as well as all electrons, are treated quantum mechanically to include nuclear quantum effects such as zero point energy and hydrogen tunneling. This approach is computationally practical and is applicable to a wide range of chemical reactions.

Research in this group spans the areas of chemistry, physics, biology, and computer science. This interdisciplinary training prepares students for a wide range of career opportunities.