w/ Dr. John Hempel
University of Pittsburgh
we are currently focusing on examining the hydride transfer mechanism in several classes of ALDH. The hydride transfer reaction in this enzyme may originate from a very unstable thiohemiacetal intermediate or possibly involve concerted proton transfer events. Which of these two mechanisms is correct greatly affects the interpretation of structure-function relationships in this enzyme and may offer an atomic rationale for various metabolic diseases. Proton and hydride quantum dynamical effects (tunneling) may also play a role.
2002: What Happens at the Active Site
2007: Strange Action at the Active Site

w/ Dr. Martin Field
Institut de Biologie Structurale
we are calculating Quantum Mechanical reference data on a large ensemble of molecules that will be utilized to develop new semiempirical molecular orbital (SMO) parameters and methods. In addition, we are developing tools in DYNAMO for researchers to efficiently parameterize SMO methods to simulate specific enzymatic reactions with quantitative accuracy.